WorldWideScience

Sample records for snowmass t4 working

  1. SUMMARY REPORT OF THE INTERACTION REGION WORKING GROUP (T1) AT SNOWMASS

    Energy Technology Data Exchange (ETDEWEB)

    Markiewicz, Thomas W

    2002-09-23

    The Interaction Region Working Group (T1) at Snowmass 2001 reviewed the issues, designs, and plans of existing and proposed colliders, including hadron colliders, e{sup -} hadron colliders, e{sup +}e{sup -} and {gamma}{gamma} linear colliders, e{sup +}e{sup -} circular colliders, and muon colliders. This document summarizes the IR issues, status, and R&D plans for each project.

  2. REPORT OF THE SNOWMASS M6 WORKING GROUP ON HIGH INTENSITY PROTON SOURCES.

    Energy Technology Data Exchange (ETDEWEB)

    CHOU,W.; WEI,J.

    2001-08-14

    The M6 working group had more than 40 active participants (listed in Section 4). During the three weeks at Snowmass, there were about 50 presentations, covering a wide range of topics associated with high intensity proton sources. The talks are listed in Section 5. This group also had joint sessions with a number of other working groups, including E1 (Neutrino Factories and Muon Colliders), E5 (Fixed-Target Experiments), M1 (Muon Based Systems), T4 (Particle Sources), T5 (Beam dynamics), T7 (High Performance Computing) and T9 (Diagnostics). The M6 group performed a survey of the beam parameters of existing and proposed high intensity proton sources, in particular, of the proton drivers. The results are listed in Table 1. These parameters are compared with the requirements of high-energy physics users of secondary beams in Working Groups E1 and E5. According to the consensus reached in the E1 and E5 groups, the U.S. HEP program requires an intense proton source, a 1-4 MW Proton Driver, by the end of this decade.

  3. REPORT OF THE SNOWMASS M6 WORKING GROUP ON HIGH INTENSITY PROTON SOURCES

    International Nuclear Information System (INIS)

    CHOU, W.; WEI, J.

    2001-01-01

    The M6 working group had more than 40 active participants (listed in Section 4). During the three weeks at Snowmass, there were about 50 presentations, covering a wide range of topics associated with high intensity proton sources. The talks are listed in Section 5. This group also had joint sessions with a number of other working groups, including E1 (Neutrino Factories and Muon Colliders), E5 (Fixed-Target Experiments), M1 (Muon Based Systems), T4 (Particle Sources), T5 (Beam dynamics), T7 (High Performance Computing) and T9 (Diagnostics). The M6 group performed a survey of the beam parameters of existing and proposed high intensity proton sources, in particular, of the proton drivers. The results are listed in Table 1. These parameters are compared with the requirements of high-energy physics users of secondary beams in Working Groups E1 and E5. According to the consensus reached in the E1 and E5 groups, the U.S. HEP program requires an intense proton source, a 1-4 MW Proton Driver, by the end of this decade

  4. Higgs Working Group Report of the Snowmass 2013 Community Planning Study

    CERN Document Server

    Dawson, S; Logan, H; Qian, J; Tully, C; Van Kooten, R; Ajaib, A; Anastassov, A; Anderson, I; Bake, O; Barger, V; Barklow, T; Batell, B; Battaglia, M; Berge, S; Blondel, A; Bolognesi, S; Brau, J; Brownson, E; Cahill-Rowley, M; Calancha-Paredes, C; Chen, C -Y; Chou, W; Clare, R; Cline, D; Craig, N; Cranmer, K; de Gruttola, M; Elagin, A; Essig, R; Everett, L; Feng, E; Fujii, K; Gainer, J; Gao, Y; Gogoladze, I; Gori, S; Goncalo, R; Graf, N; Grojean, C; Guindon, S; Han, T; Hanson, G; Harnik, R; Heinemann, B; Heinemeyer, S; Heintz, U; Hewett, J; Ilchenko, Y; Ismail, A; Jain, V; Janot, P; Kawada, S; Kehoe, R; Klute, M; Kotwal, A; Krueger, K; Kukartsev, G; Kumar, K; Kunkle, J; Lewis, I; Li, Y; Linssen, L; Lipeles, E; Lipton, R; Liss, T; List, J; Liu, T; Liu, Z; Low, I; Ma, T; Mackenzie, P; Mellado, B; Melnikov, K; Moortgat-Pick, G; Mourou, G; Narain, M; Nielsen, J; Okada, N; Okawa, H; Olsen, J; Onyisi, P; Parashar, N; Peskin, M; Petriello, F; Plehn, T; Pollard, C; Potter, C; Prokofiev, K; Rauch, M; Rizzo, T; Robens, T; Rodriguez, V; Roloff, P; Ruiz, R; Sanz, V; Sayre, J; Shafi, Q; Shaughnessy, G; Sher, M; Simon, F; Solyak, N; Stupak, J; Su, S; Tanabe, T; Tajima, T; Telnov, V; Tian, J; Thomas, S; Thomson, M; Un, C; Velasco, M; Wagner, C; Wang, S; Whitbeck, A; Yao, W; Yokoya, H; Zenz, S; Zerwas, D; Zhang, Y; Zhou, Y

    2013-01-01

    This report summarizes the work of the Energy Frontier Higgs Boson working group of the 2013 Community Summer Study (Snowmass). We identify the key elements of a precision Higgs physics program and document the physics potential of future experimental facilities as elucidated during the Snowmass study. We study Higgs couplings to gauge boson and fermion pairs, double Higgs production for the Higgs self-coupling, its quantum numbers and $C\\!P$-mixing in Higgs couplings, the Higgs mass and total width, and prospects for direct searches for additional Higgs bosons in extensions of the Standard Model. Our report includes projections of measurement capabilities from detailed studies of the Compact Linear Collider (CLIC), a Gamma-Gamma Collider, the International Linear Collider (ILC), the Large Hadron Collider High-Luminosity Upgrade (HL-LHC), Very Large Hadron Colliders up to 100 TeV (VLHC), a Muon Collider, and a Triple-Large Electron Positron Collider (TLEP).

  5. SNOWMASS (DPF Community Summer Study)

    Energy Technology Data Exchange (ETDEWEB)

    Cronin-Hennessy, et al, Daniel

    2013-08-06

    The 2013 Community Summer Study, known as Snowmass," brought together nearly 700 physicists to identify the critical research directions for the United States particle physics program. Commissioned by the American Physical Society, this meeting was the culmination of intense work over the past year by more than 1000 physicists that defined the most important questions for this field and identified the most promising opportunities to address them. This Snowmass study report is a key resource for setting priorities in particle physics.

  6. Supercollider at Snowmass

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-11-15

    While the proposed US Superconducting Supercollider – SSC, an 85 kilometre ring t o provide 20 000 GeV (20 TeV) proton beams – waits hopefully for the go-ahead, the US physics community is preparing for life at the supercollider. A Summer Study on SSC physics was held at Snowmass Village, Colorado, this summer. The principal goal was the critical evaluation of all aspects of the SSC, in the light of the recently submitted Conceptual Design Report, and of progress in accelerator technology, collider physics, and instrumentation.

  7. Supercollider at Snowmass

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    While the proposed US Superconducting Supercollider – SSC, an 85 kilometre ring t o provide 20 000 GeV (20 TeV) proton beams – waits hopefully for the go-ahead, the US physics community is preparing for life at the supercollider. A Summer Study on SSC physics was held at Snowmass Village, Colorado, this summer. The principal goal was the critical evaluation of all aspects of the SSC, in the light of the recently submitted Conceptual Design Report, and of progress in accelerator technology, collider physics, and instrumentation

  8. Overview and charge - Snowmass Workshop 2005

    International Nuclear Information System (INIS)

    Berger, E. L.

    2006-01-01

    This contribution to the published Proceedings records the opening talk I presented on the first morning of the 2005 International Linear Collider Workshop in Snowmass, CO, August 14 - 27, 2005. It includes a summary of the motivation for the workshop, the scientific goals and charges for the working groups, the initial plans of the accelerator, detector, and physics groups, and the activities of the communication, education, and outreach group. This document also describes organizational aspects of the meeting, particularly the scientific committee structure, the self-organization of the working groups, the composition of the indispensable secretariat and computer support teams, and the sources of funding support. The report serves as an introduction to the proceedings whose individual papers and summary documents must be consulted for an appreciation of the accomplishments and progress made at Snowmass in 2005 toward the realization of an International Linear Collider

  9. EXECUTIVE SUMMARY OF THE SNOWMASS 2001 WORKING GROUP : ELECTROWEAK SYMMETRY BREAKING

    International Nuclear Information System (INIS)

    CARENA, M.; GERDES, D.W.; HABER, H.E.; TURCOT, A.S.; ZERWAS, P.M.

    2001-01-01

    In this summary report of the 2001 Snowmass Electroweak Symmetry Breaking Working Group, the main candidates for theories of electroweak symmetry breaking are surveyed, and the criteria for distinguishing among the different approaches are discussed. The potential for observing electroweak symmetry breaking phenomena at the upgraded Tevatron and the LHC is described. We emphasize the importance of a high-luminosity e + e - linear collider for precision measurements to clarify the underlying electroweak symmetry breaking dynamics. Finally, we note the possible roles of the μ + μ - collider and VLHC for further elucidating the physics of electroweak symmetry breaking

  10. Snowmass Fusion Summer Study Group workshop

    International Nuclear Information System (INIS)

    Clement, S.

    1999-01-01

    The Snowmass Fusion Summer Study Group workshop, has taken place at Snowmass, Colorado, 11-23 July 1999. Its purpose was to discuss opportunities and directions in fusion energy science for the next decade. About 300 experts from all fields in the magnetic and inertial fusion communities attended, coming mostly from the US, but with some foreign participation

  11. Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 4: Cosmic Frontier

    Energy Technology Data Exchange (ETDEWEB)

    Feng, J. L. [MIT, LNS; Ritz, S. [UC, Santa Cruz; Beatty, J. J. [Ohio State U.; Buckley, J. [Washington U., Seattle; Cowen, D. F. [Penn State U.; Cushman, P. [Minnesota U.; Dodelson, S. [Chicago U., Astron. Astrophys. Ctr.; Galbiati, C. [PNPI, CSTD; Honscheid, K. [Ohio State U.; Hooper, D. [Chicago U., Astron. Astrophys. Ctr.; Kaplinghat, M. [UC, Irvine; Kusenko, A. [Unlisted; Matchev, K. [Florida U.; McKinsey, D. [Yale U.; Nelson, A. E. [Washington U., Seattle; Olinto, A. [Chicago U., EFI; Profumo, S. [UC, Santa Cruz; Robertson, H. [Washington U., Seattle; Rosenberg, L. [Unlisted; Sinnis, G. [Los Alamos; Tait, T. M.P. [UCLA

    2014-01-23

    These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 4, on the Cosmic Frontier, discusses the program of research relevant to cosmology and the early universe. This area includes the study of dark matter and the search for its particle nature, the study of dark energy and inflation, and cosmic probes of fundamental symmetries.

  12. Snowmass 2002: The Fusion Energy Sciences Summer Study

    International Nuclear Information System (INIS)

    Sauthoff, N.; Navratil, G.; Bangerter, R.

    2002-01-01

    will present a uniform technical assessment of the benefits of the three approaches. The draft report will be presented and extensively discussed during the July meeting, leading to a final report. This report will provide critical fusion community input to the decision process of FESAC and DOE in 2002-2003, and to the review of burning plasma science by the National Academy of Sciences called for by FESAC and Energy Legislation which was passed by the House of Representatives [H.R. 4]. Members of the fusion community are encouraged to participate in the Snowmass working groups

  13. Snowmass 2002: The Fusion Energy Sciences Summer Study; TOPICAL

    International Nuclear Information System (INIS)

    N. Sauthoff; G. Navratil; R. Bangerter

    2002-01-01

    present a uniform technical assessment of the benefits of the three approaches. The draft report will be presented and extensively discussed during the July meeting, leading to a final report. This report will provide critical fusion community input to the decision process of FESAC and DOE in 2002-2003, and to the review of burning plasma science by the National Academy of Sciences called for by FESAC and Energy Legislation which was passed by the House of Representatives[H.R. 4]. Members of the fusion community are encouraged to participate in the Snowmass working groups

  14. 2001 Snowmass Accelerator R and D Report

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Alex W.

    2002-08-30

    The purpose of this report is to provide a perspective on future accelerator projects, and to identify the R&D activities necessary to prepare for these projects. The report summarizes the conclusions of accelerator studies made during the 2001 Snowmass Summer Study on the Future of Particle Physics. In doing so, it serves as a summary of the opinions on accelerator R&D expressed by the scientific community as it looks towards the next few decades. The main technical content is provided by the Executive Summaries of each of the fifteen accelerator Working Groups. These Working Group Executive Summaries form an integral part of this report.

  15. 2001 Snowmass Accelerator R and D Report

    International Nuclear Information System (INIS)

    Chao, Alex W.

    2002-01-01

    The purpose of this report is to provide a perspective on future accelerator projects, and to identify the R and D activities necessary to prepare for these projects. The report summarizes the conclusions of accelerator studies made during the 2001 Snowmass Summer Study on the Future of Particle Physics. In doing so, it serves as a summary of the opinions on accelerator R and D expressed by the scientific community as it looks towards the next few decades. The main technical content is provided by the Executive Summaries of each of the fifteen accelerator Working Groups. These Working Group Executive Summaries form an integral part of this report

  16. Snowmass 2013 Young Physicists Science and Career Survey Report

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, J. [Fermilab; Asaadi, J. [Syracuse U.; Carls, B. [Fermilab; Cotta, R. [UC, Irvine; Guenette, R. [Yale U.; Kiburg, B. [Fermilab; Kobach, A. [Northwestern U.; Lippincott, H. [Fermilab; Littlejohn, B. [Cincinnati U.; Love, J. [Argonne; Penning, B. [Fermilab; Santos, M. Soares [Fermilab; Strauss, T. [thomas.strauss@lhep.unibe.ch; Szelc, A. [Yale U.; Worcester, E. [Brookhaven; Yu, F. [Fermilab

    2013-07-30

    From April to July 2013 the Snowmass Young Physicists (SYP) administered an online survey collecting the opinions and concerns of the High Energy Physics (HEP) community. The aim of this survey is to provide input into the long term planning meeting known as the Community Summer Study (CSS), or Snowmass on the Mississippi. In total, 1112 respondents took part in the survey including 74 people who had received their training within HEP and have since left for non-academic jobs. This paper presents a summary of the survey results including demographic, career outlook, planned experiments and non-academic career path information collected.

  17. Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 1: Summary

    Energy Technology Data Exchange (ETDEWEB)

    Rosner, J.L.; et al.

    2014-01-23

    These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 1 contains the Executive Summary and the summaries of the reports of the nine working groups.

  18. Little Higgs model limits from LHC - Input for Snowmass 2013

    International Nuclear Information System (INIS)

    Reuter, Juergen; Tonini, Marco; Vries, Maikel de

    2013-07-01

    The status of the most prominent model implementations of the Little Higgs paradigm, the Littlest Higgs with and without discrete T parity as well as the Simplest Little Higgs are reviewed. For this, we are taking into account a fit to 21 electroweak precision observables from LEP, SLC, Tevatron together with the full 25 fb -1 of Higgs data reported from ATLAS and CMS at Moriond 2013. We also - focusing on the Littlest Higgs with T parity - include an outlook on corresponding direct searches at the 8 TeV LHC and their competitiveness with the EW and Higgs data regarding their exclusion potential. This contribution to the Snowmass procedure serves as a guideline which regions in parameter space of Little Higgs models are still compatible for the upcoming LHC runs and future experiments at the energy frontier. For this we propose two different benchmark scenarios for the Littlest Higgs with T parity, one with heavy mirror quarks, one with light ones.

  19. Little Higgs model limits from LHC - Input for Snowmass 2013

    Energy Technology Data Exchange (ETDEWEB)

    Reuter, Juergen; Tonini, Marco; Vries, Maikel. de

    2013-07-15

    The status of the most prominent model implementations of the Little Higgs paradigm, the Littlest Higgs with and without discrete T parity as well as the Simplest Little Higgs are reviewed. For this, we are taking into account a fit to 21 electroweak precision observables from LEP, SLC, Tevatron together with the full 25 fb{sup -1} of Higgs data reported from ATLAS and CMS at Moriond 2013. We also - focusing on the Littlest Higgs with T parity - include an outlook on corresponding direct searches at the 8 TeV LHC and their competitiveness with the EW and Higgs data regarding their exclusion potential. This contribution to the Snowmass procedure serves as a guideline which regions in parameter space of Little Higgs models are still compatible for the upcoming LHC runs and future experiments at the energy frontier. For this we propose two different benchmark scenarios for the Littlest Higgs with T parity, one with heavy mirror quarks, one with light ones.

  20. Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 8: Instrumentation Frontier

    Energy Technology Data Exchange (ETDEWEB)

    Demarteau, M; Lipton, R; Nicholson, H; Shipsey, I; Akerib, D; Albayrak-Yetkin, A; Alexander, J; Anderson, J; Artuso, M; Asner, D; Ball, R; Battaglia, M; Bebek, C; Beene, J; Benhammou, Y; Bentefour, E; Bergevin, M; Bernstein, A; Bilki, B; Blucher, E; Bolla, G; Bortoletto, D; Bowden, N; Brooijmans, G; Byrum, K; Cabrera, B; Cancelo, G; Carlstrom, J; Casey, B; Chang, C; Chapman, J; Chen, CH; Childres, I; Christian, D; Convery, M; Corso, WCJ; Cumalat, J; Cushman, P; Via, CD; Dazeley, S; Debbins, P; Deptuch, G; Dhawan, S; Benedetto, VD; DiGiovene, B; Djurcic, Z; Dye, S; Elagin, A; Estrada, J; Evans, H; Etzion, E; Fast, J; Ferretti, C; Fisher, P; Fleming, B; Francis, K; Friedman, P; Frisch, H; Garcia-Sciveres, M; Gatto, C; Geronim, G; Gilchriese, G; Golwala, S; Grant, C; Grillo, A; Grünendahl, E; Gorham, P; Guan, L; Gutierrez, G; Haber, C; Hall, J; Haller, G; Hast, C; Heintz, U; Hemmick, T; Hitlin, DG; Hogan, C; Hohlmann, M; Hoppe, E; Hsu, L; Huffer, M; Irwin, K; Izraelevitch, F; Jennings, G; Johnson, M; Jung, A; Kagan, H; Kenney, C; Kettell, S; Khanna, R; Khristenko, V; Krennrich, F; Kuehn, K; Kutschke, R; Learned, J; Lee, AT; Levin, D; Liu, T; Liu, ATK; Lissauer, D; Love, J; Lynn, D; MacFarlane, D; Magill, S; Majewski, S; Mans, J; Maricic, J; Marleau, P; Mazzacane, A; McKinsey, D; Mehl, J; Mestvirisvilli, A; Meyer, S; Mokhov, N; Moshe, M; Mukherjee, A; Murat, P; Nahn, S; Narain, M; Nadel-Turonski, P; Newcomer, M; Nishimura, K; Nygren, D; Oberla, E; Onel, Y; Oreglia, M; Orrell, J; Paley, J; Para, A; Parker, S; Polychronakos, V; Pordes, S; Privitera, P; Prosser, A; Pyle, M; Raaf, J; Ramberg, E; Rameika, R; Rebel, B; Repond, J; Reyna, D; Ristori, L; Rivera, R; Ronzhin, A; Rusack, R; Russ, J; Ryd, A; Sadrozinski, H; Sahoo, H; Sanchez, MC; Sanzeni, C; Schnetzer, S; Seidel, S; Seiden, A; Schmidt, I; Shenai, A; Shutt, T; Silver, Y; Smith, W; Snowden-Ifft, D; Sonnenschein, A; Southwick, D; Spiegel, L; Stanitzki, M; Striganov, S; Su, D; Sumner, R; Svoboda, R; Sweany, M; Talaga, R; Tayloe, R; Tentindo, S; Terentiev, N; Thom-Levy, J; Thorn, C; Tiffenberg, J; Trischuk, W; Tschirhart, R; Turner, M; Underwood, D; Uplegger, L; Urheim, J; Vagins, M; Bibber, KV; Varner, G; Varner, R; Va' vra, J; Lippe, HVD; Wagner, R; Wagner, S; Weaverdyck, C; Wenzel, H; Weinstein, A; Wetstein, M; White, A; Wigman, R; Wilson, P; Winn, D; Winter, P; Woody, C; Xia, L; Xie, JQ; Ye, Z; Yeh, MF; Yetkin, T; Yoo, JH; Yu, J; Yu, JM; Zeller, S; Zhang, JL; Zhu, JJ; Zhou, B; Zhu, RY; Zitzer, B

    2014-01-23

    These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 8, on the Instrumentation Frontier, discusses the instrumentation needs of future experiments in the Energy, Intensity, and Cosmic Frontiers, promising new technologies for particle physics research, and issues of gathering resources for long-term research in this area.

  1. Summary of the TeV33 working group

    International Nuclear Information System (INIS)

    Bagley, P.P.; Bieniosek, F.M.; Colestock, P.

    1996-10-01

    This summary of the TeV33 working group at Snowmass reports on work in the areas of Tevatron store parameters, the beam-beam interaction, Main Injector intensity (slip stacking), antiproton production, and electron cooling

  2. Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 3: Energy Frontier

    Energy Technology Data Exchange (ETDEWEB)

    Brock, R.; et al.

    2014-01-23

    These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 3, on the Energy Frontier, discusses the program of research with high-energy colliders. This area includes experiments on the Higgs boson, the electroweak and strong interactions, and the top quark. It also encompasses direct searches for new particles and interactions at high energy.

  3. Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 10: Communication, Education, and Outreach

    OpenAIRE

    Bardeen, M.; Cronin-Hennessy, D.; Barnett, R. M.; Bhat, P.; Cecire, K.; Cranmer, K.; Jordan, T.; Karliner, I.; Lykken, J.; Norris, P.; White, H.; Yurkewicz, K.

    2014-01-01

    These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 10, on Communication, Education, and Outreach, discusses the resources and issues for the communication of information about particle physics to teachers and students, to scientists in other fields, to policy makers, and to the general public.

  4. Working Group Report: Neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    de Gouvea, A.; Pitts, K.; Scholberg, K.; Zeller, G. P. [et al.

    2013-10-16

    This document represents the response of the Intensity Frontier Neutrino Working Group to the Snowmass charge. We summarize the current status of neutrino physics and identify many exciting future opportunities for studying the properties of neutrinos and for addressing important physics and astrophysics questions with neutrinos.

  5. Working Group Report: Higgs Boson

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Sally; Gritsan, Andrei; Logan, Heather; Qian, Jianming; Tully, Chris; Van Kooten, Rick [et al.

    2013-10-30

    This report summarizes the work of the Energy Frontier Higgs Boson working group of the 2013 Community Summer Study (Snowmass). We identify the key elements of a precision Higgs physics program and document the physics potential of future experimental facilities as elucidated during the Snowmass study. We study Higgs couplings to gauge boson and fermion pairs, double Higgs production for the Higgs self-coupling, its quantum numbers and $CP$-mixing in Higgs couplings, the Higgs mass and total width, and prospects for direct searches for additional Higgs bosons in extensions of the Standard Model. Our report includes projections of measurement capabilities from detailed studies of the Compact Linear Collider (CLIC), a Gamma-Gamma Collider, the International Linear Collider (ILC), the Large Hadron Collider High-Luminosity Upgrade (HL-LHC), Very Large Hadron Colliders up to 100 TeV (VLHC), a Muon Collider, and a Triple-Large Electron Positron Collider (TLEP).

  6. Numerical modeling of the Snowmass Creek paleoglacier, Colorado, and climate in the Rocky Mountains during the Bull Lake glaciation (MIS 6)

    Energy Technology Data Exchange (ETDEWEB)

    Eric M. Leonard; Mitchell A. Plummer; Paul E. Carrara

    2014-04-01

    Well-preserved moraines from the penultimate, or Bull Lake, glaciation of Snowmass Creek Valley in the Elk Range of Colorado present an opportunity to examine the character of the high-altitude climate in the Rocky Mountains during Marine Oxygen Isotope Stage 6. This study employs a 2-D coupled mass/energy balance and flow model to assess the magnitudes of temperature and precipitation change that could have sustained the glacier in mass-balance equilibrium at its maximum extent during the Bull Lake glaciation. Variable substrate effects on glacier flow and ice thickness make the modeling somewhat more complex than in geologically simpler settings. Model results indicate that a temperature depression of about 6.7°C compared with the present (1971–2000 AD) would have been necessary to sustain the Snowmass Creek glacier in mass-balance equilibrium during the Bull Lake glaciation, assuming no change in precipitation amount or seasonality. A 50% increase or decrease from modern precipitation would have been coupled with 5.2°C and 9.1°C Bull Lake temperature depressions respectively. Uncertainty in these modeled temperature depressions is about 1°C.

  7. Online community marketing of ski resorts : an in-depth best practice study of aspen/snowmass and breckenridge ski resort

    OpenAIRE

    Kráľ, Branislav

    2013-01-01

    Online brand community is a novel phenomenon that carries a number of benefits, but lack of clarity in antecedents of its effectiveness as a marketing alternative. Aspen/Snowmass and Breckenridge Ski Resort are two leading players in the ski industry, and this paper analyzes their activity in-depth in order to bring clarity by extracting implications on best practice. For the purpose, a tailor-made methodology is constructed. It consists of combining two analytical frameworks, interviews with...

  8. 216-T-4 interim stabilization final report

    International Nuclear Information System (INIS)

    Smith, D.L.

    1996-01-01

    This report provides a general description of the activities performed for the interim stabilization of the 216-T-4-1 ditch, 216-T-4-2 ditch, and 216-T-4-2 pond. Interim stabilization was required to reduce the amount of surface-contaminated acres and to minimize the migration of radioactive contamination. Work associated with the 216-T4-1 ditch and 216-T-4-2 pond was performed by the Radiation Area Remedial Action (RARA) Project. Work associated with the 216-T-4-2 ditch was done concurrently but was funded by Westinghouse Hanford Company (WHC) Tank Waste Remediation Systems (TWRS)

  9. A geochronologic framework for the Ziegler Reservoir fossil site, Snowmass Village, Colorado

    Science.gov (United States)

    Mahan, Shannon; Gray, Harrison J.; Pigati, Jeffrey S.; Wilson, Jim; Lifton, Nathaniel A.; Paces, James B.; Blaauw, Maarten

    2014-01-01

    The Ziegler Reservoir fossil site near Snowmass Village, Colorado, provides a unique opportunity to reconstruct high-altitude paleoenvironmental conditions in the Rocky Mountains during the last interglacial period. We used four different techniques to establish a chronological framework for the site. Radiocarbon dating of lake organics, bone collagen, and shell carbonate, and in situ cosmogenic 10Be and 26Al ages on a boulder on the crest of a moraine that impounded the lake suggest that the ages of the sediments that hosted the fossils are between ~ 140 ka and > 45 ka. Uranium-series ages of vertebrate remains generally fall within these bounds, but extremely low uranium concentrations and evidence of open-system behavior limit their utility. Optically stimulated luminescence (OSL) ages (n = 18) obtained from fine-grained quartz maintain stratigraphic order, were replicable, and provide reliable ages for the lake sediments. Analysis of the equivalent dose (DE) dispersion of the OSL samples showed that the sediments were fully bleached prior to deposition and low scatter suggests that eolian processes were likely the dominant transport mechanism for fine-grained sediments into the lake. The resulting ages show that the fossil-bearing sediments span the latest part of marine isotope stage (MIS) 6, all of MIS 5 and MIS 4, and the earliest part of MIS 3.

  10. Simplified models for new physics in vector boson scattering. Input for Snowmass 2013

    International Nuclear Information System (INIS)

    Reuter, Juergen; Kilian, Wolfgang; Sekulla, Marco

    2013-07-01

    In this contribution to the Snowmass process 2013 we give a brief review of how new physics could enter in the electroweak (EW) sector of the Standard Model (SM). This new physics, if it is directly accessible at low energies, can be parameterized by explicit resonances having certain quantum numbers. The extreme case is the decoupling limit where those resonances are very heavy and leave only traces in the form of deviations in the SM couplings. Translations are given into higher-dimensional operators leading to such deviations. As long as such resonances are introduced without a UV-complete theory behind it, these models suffer from unitarity violation of perturbative scattering amplitudes. We show explicitly how theoretically sane descriptions could be achieved by using a unitarization prescription that allows a correct description of such a resonance without specifying a UV-complete model.

  11. Simplified models for new physics in vector boson scattering. Input for Snowmass 2013

    Energy Technology Data Exchange (ETDEWEB)

    Reuter, Juergen [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kilian, Wolfgang; Sekulla, Marco [Siegen Univ. (Germany). Theoretische Physik I

    2013-07-15

    In this contribution to the Snowmass process 2013 we give a brief review of how new physics could enter in the electroweak (EW) sector of the Standard Model (SM). This new physics, if it is directly accessible at low energies, can be parameterized by explicit resonances having certain quantum numbers. The extreme case is the decoupling limit where those resonances are very heavy and leave only traces in the form of deviations in the SM couplings. Translations are given into higher-dimensional operators leading to such deviations. As long as such resonances are introduced without a UV-complete theory behind it, these models suffer from unitarity violation of perturbative scattering amplitudes. We show explicitly how theoretically sane descriptions could be achieved by using a unitarization prescription that allows a correct description of such a resonance without specifying a UV-complete model.

  12. Linear Collider Working Group reports from Snowmass '88

    International Nuclear Information System (INIS)

    Ruth, R.D.

    1989-03-01

    This report contains a summary of the Linear Collider Working Group. Papers on the following topics are discussed: parameters; damping ring; bunch compressor; linac; final focus; and multibunch effects

  13. A high-elevation, multi-proxy biotic and environmental record of MIS 6-4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA

    Science.gov (United States)

    Miller, Ian M.; Pigati, Jeffrey S.; Anderson, R. Scott; Johnson, Kirk R.; Mahan, Shannon; Ager, Thomas A.; Baker, Richard G.; Blaauw, Maarten; Bright, Jordon; Brown, Peter M.; Bryant, Bruce; Calamari, Zachary T.; Carrara, Paul E.; Michael D., Cherney; Demboski, John R.; Elias, Scott A.; Fisher, Daniel C.; Gray, Harrison J.; Haskett, Danielle R.; Honke, Jeffrey S.; Jackson, Stephen T.; Jiménez-Moreno, Gonzalo; Kline, Douglas; Leonard, Eric M.; Lifton, Nathaniel A.; Lucking, Carol; McDonald, H. Gregory; Miller, Dane M.; Muhs, Daniel R.; Nash, Stephen E.; Newton, Cody; Paces, James B.; Petrie, Lesley; Plummer, Mitchell A.; Porinchu, David F.; Rountrey, Adam N.; Scott, Eric; Sertich, Joseph J. W.; Sharpe, Saxon E.; Skipp, Gary L.; Strickland, Laura E.; Stucky, Richard K.; Thompson, Robert S.; Wilson, Jim

    2014-01-01

    In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~ 140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

  14. Report of the Quark Flavor Physics Working Group

    CERN Document Server

    Butler, J N; Ritchie, J L; Cirigliano, V; Kettell, S; Briere, R; Petrov, A A; Schwartz, A; Skwarnicki, T; Zupan, J; Christ, N; Sharpe, S R; Van de Water, R S; Altmannshofer, W; Arkani-Hamed, N; Artuso, M; Asner, D M; Bernard, C; Bevan, A J; Blanke, M; Bonvicini, G; Browder, T E; Bryman, D A; Campana, P; Cenci, R; Cline, D; Comfort, J; Cronin-Hennessy, D; Datta, A; Dobbs, S; Duraisamy, M; El-Khadra, A X; Fast, J E; Forty, R; Flood, K T; Gershon, T; Grossman, Y; Hamilton, B; Hill, C T; Hill, R J; Hitlin, D G; Jaffe, D E; Jawahery, A; Jessop, C P; Kagan, A L; Kaplan, D M; Kohl, M; Krizan, P; Kronfeld, A S; Lee, K; Littenberg, L S; MacFarlane, D B; Mackenzie, P B; Meadows, B T; Olsen, J; Papucci, M; Parsa, Z; Paz, G; Perez, G; Piilonen, L E; Pitts, K; Purohit, M V; Quinn, B; Ratcliff, B N; Roberts, D A; Rosner, J L; Rubin, P; Seeman, J; Seth, K K; Schmidt, B; Schopper, A; Sokoloff, M D; Soni, A; Stenson, K; Stone, S; Sundrum, R; Tschirhart, R; Vainshtein, A; Wah, Y W; Wilkinson, G; Wise, M B; Worcester, E; Xu, J; Yamanaka, T

    2013-01-01

    This report represents the response of the Intensity Frontier Quark Flavor Physics Working Group to the Snowmass charge. We summarize the current status of quark flavor physics and identify many exciting future opportunities for studying the properties of strange, charm, and bottom quarks. The ability of these studies to reveal the effects of new physics at high mass scales make them an essential ingredient in a well-balanced experimental particle physics program.

  15. A high-elevation, multi-proxy biotic and environmental record of MIS 6–4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA

    Energy Technology Data Exchange (ETDEWEB)

    Ian M. Miller; Mitchell A. Plummer; Various Others

    2014-10-01

    In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5

  16. Report of the 2005 Snowmass Top/QCD Working Group

    Energy Technology Data Exchange (ETDEWEB)

    Juste, A.; /Fermilab; Kiyo, Y.; /Aachen, Tech. Hochsch.; Petriello, F.; /Wisconsin U., Madison /Fermilab; Teubner, T.; /Liverpool U., Dept. Math.; Agashe, K.; Batra, P.; Baur, U.; Berger, C.F.; Cembranos, J.A.R.; Gehrmann-De Ridder, A.; Gehrmann, T.; Glover, E.W.N.; Godfrey, S.; Hoang, A.; Perelstein, M.; Sullivan, Z.; Tait, T.; Zhu, S.; /Johns

    2006-01-17

    This report discusses several topics in both top quark physics and QCD at an International Linear Collider (ILC). Issues such as measurements at the t tbar threshold, including both theoretical and machine requirements, and the determination of electroweak top quark couplings are reviewed. New results concerning the potential of a 500 GeV e+e collider for measuring Wtb couplings and the top quark Yukawa coupling are presented. The status of higher order QCD corrections to jet production cross sections, heavy quark form factors, and longitudinal gauge boson scattering, needed for percent-level studies at the ILC, are reviewed. A new study of the measurement of the hadronic structure of the photon at a gamma gamma collider is presented. The effects on top quark properties from several models of new physics, including composite models, Little Higgs theories, and CPT violation, are studied.

  17. LINEAR COLLIDER PHYSICS RESOURCE BOOK FOR SNOWMASS 2001

    International Nuclear Information System (INIS)

    ABE, T.; DAWSON, S.; HEINEMEYER, S.; MARCIANO, W.; PAIGE, F.; TURCOT, A.S.; ET

    2001-01-01

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e + e - linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e + e - linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e + e - linear collider; in any scenario that is now discussed, physics will benefit from the new information that e + e - experiments can provide

  18. LINEAR COLLIDER PHYSICS RESOURCE BOOK FOR SNOWMASS 2001.

    Energy Technology Data Exchange (ETDEWEB)

    ABE,T.; DAWSON,S.; HEINEMEYER,S.; MARCIANO,W.; PAIGE,F.; TURCOT,A.S.; ET AL

    2001-05-03

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e{sup +}e{sup {minus}} linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e{sup +}e{sup {minus}} linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e{sup +}e{sup {minus}} linear collider; in any scenario that is now discussed, physics will benefit from the new information that e{sup +}e{sup {minus}} experiments can provide.

  19. Linear Collider Physics Resource Book for Snowmass 2001

    Energy Technology Data Exchange (ETDEWEB)

    Peskin, Michael E

    2001-06-05

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e{sup +}e{sup -} linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e{sup +}e{sup -} linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e{sup +}e{sup -} linear collider; in any scenario that is now discussed, physics will benefit from the new information that e{sup +}e{sup -} experiments can provide.

  20. An Evaluation of Thyroid Hormones (T4, T3, and Free T4) Concentrations During Pregnancy

    International Nuclear Information System (INIS)

    Lee, Kyu Bo; Kim, Ji Yeul

    1981-01-01

    Serum concentrations of T 4 , T 3 , and free T 4 were measured by radioimmunoassay in normal pregnant women at trimesters, in postpartum women, and cord blood of neonate. Total T 4 were increased during pregnancy, remarkably high in the first trimester, and also somewhat increased in postpartum, and normal in neonate. Total T 3 were in normal range during pregnancy, but increased in postpartum, whereas decreased in neonate. Free T 4 were decreased in 2nd and 3rd trimesters of pregnancy, however normal in postpartum and neonate.

  1. Working Group Report: Quantum Chromodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, J. M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2013-10-18

    This is the summary report of the energy frontier QCD working group prepared for Snowmass 2013. We review the status of tools, both theoretical and experimental, for understanding the strong interactions at colliders. We attempt to prioritize important directions that future developments should take. Most of the efforts of the QCD working group concentrate on proton-proton colliders, at 14 TeV as planned for the next run of the LHC, and for 33 and 100 TeV, possible energies of the colliders that will be necessary to carry on the physics program started at 14 TeV. We also examine QCD predictions and measurements at lepton-lepton and lepton-hadron colliders, and in particular their ability to improve our knowledge of strong coupling constant and parton distribution functions.

  2. Introns in the genome of bacteriophage T4

    International Nuclear Information System (INIS)

    Gott, J.M.

    1987-01-01

    RNA from T4-infected cells yields multiple end-labeled species when incubated with [α- 32 P]GTP under self-splicing conditions. One of these corresponds to the previously characterized intron from the T4 td gene and, as shown in this work, the others represent additional group I introns in T4. Two loci distinct from the td gene were found to hybridize to the mixed GTP-labeled T4 RNA probe. These were mapped to the unlinked genes nrdB and sunY. Cloned DNA from the nrdB region that contained the intron was shown to generate characteristic group I splice products with RNA synthesized in vivo or in vitro. The splice junction of the nrdB gene was determined and the nature of the RNA reaction products characterized. In vivo expression of the nrdB gene and the open reading frame within the intron was studied using in-frame lacZ fusions and primer extension analyses. The data suggest that expression of the intron open reading frame is highly regulated during T4 infection. Possible regulatory mechanisms are discussed

  3. Summary of the Snowmastodon Project Special Volume. A high-elevation, multi-proxy biotic and environmental record of MIS 6-4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA

    Science.gov (United States)

    Miller, Ian M.; Pigati, Jeffrey S.; Scott Anderson, R.; Johnson, Kirk R.; Mahan, Shannon A.; Ager, Thomas A.; Baker, Richard G.; Blaauw, Maarten; Bright, Jordon; Brown, Peter M.; Bryant, Bruce; Calamari, Zachary T.; Carrara, Paul E.; Cherney, Michael D.; Demboski, John R.; Elias, Scott A.; Fisher, Daniel C.; Gray, Harrison J.; Haskett, Danielle R.; Honke, Jeffrey S.; Jackson, Stephen T.; Jiménez-Moreno, Gonzalo; Kline, Douglas; Leonard, Eric M.; Lifton, Nathaniel A.; Lucking, Carol; Gregory McDonald, H.; Miller, Dane M.; Muhs, Daniel R.; Nash, Stephen E.; Newton, Cody; Paces, James B.; Petrie, Lesley; Plummer, Mitchell A.; Porinchu, David F.; Rountrey, Adam N.; Scott, Eric; Sertich, Joseph J. W.; Sharpe, Saxon E.; Skipp, Gary L.; Strickland, Laura E.; Stucky, Richard K.; Thompson, Robert S.; Wilson, Jim

    2014-11-01

    In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean-atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010-2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~ 140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

  4. Thyroxine (T 4-RIA) and triiodothyronine (T 3-RIA) serum levels in sheep fed on Leucaena Leucocephala; Niveis sericos de tiroxina (T4-RIA) e triiodotinonina (T3-RIA) em ovinos alimentados cm Leucaena Leucocephala LAM

    Energy Technology Data Exchange (ETDEWEB)

    Pessoa, J M; Rodriguez, N M [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Escola de Veterinaria; Cardoso, W M [Maranhao Univ., Sao Luis, MA (Brazil). Escola de Medicina Veterinaria; Velez, C E.S.

    1988-12-31

    The aim of this work is to study the toxicity of Leucaena leucocephala on thyroxine and triiodothyronine serum concentration. Results indicate that ovine T 4 and T 3 serum levels do not decrease with Leucaena leucocephala feeding, sohen proreided for 41 days. (author). 10 refs, 1 tab.

  5. CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells

    Science.gov (United States)

    Aguado, Enrique; Garcia-Cozar, Francisco

    2014-01-01

    Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127lowPD-1highTIM-3high regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein. PMID:24465502

  6. CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Cecilia Fernandez-Ponce

    Full Text Available Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127(lowPD-1(highTIM-3(high regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein.

  7. Experiments at future hadron colliders

    International Nuclear Information System (INIS)

    Paige, F.E.

    1991-01-01

    This report summarizes signatures and backgrounds for processes in high-energy hadronic collisions, particularly at the SSC. It includes both signatures for new particles -- t quarks, Higgs bosons, new Ζ' bosons, supersymmetric particles, and technicolor particles -- and other experiments which might be done. It is based on the 1990 Snowmass Workshop and on work contained in the Expressions of Interest submitted to the SSC. 46 refs., 19 figs., 1 tab

  8. Thyroxine (T 4-RIA) and triiodothyronine (T 3-RIA) serum levels in sheep fed on Leucaena Leucocephala

    International Nuclear Information System (INIS)

    Pessoa, J.M.; Rodriguez, N.M.; Cardoso, W.M.; Velez, C.E.S.

    1988-01-01

    The aim of this work is to study the toxicity of Leucaena leucocephala on thyroxine and triiodothyronine serum concentration. Results indicate that ovine T 4 and T 3 serum levels do not decrease with Leucaena leucocephala feeding, sohen proreided for 41 days. (author). 10 refs, 1 tab

  9. Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Sarah A Wernimont

    2010-05-01

    Full Text Available T cell activation and immune synapse formation require the appropriate activation and clustering of the integrin, LFA-1. Previous work has reported that the calpain family of calcium-dependent proteases are important regulators of integrin activation and modulate T cell adhesion and migration. However, these studies have been limited by the use of calpain inhibitors, which have known off-target effects.Here, we used a LoxP/CRE system to specifically deplete calpain 4, a small regulatory calpain subunit required for expression and activity of ubiquitously expressed calpains 1 and 2, in CD4+ T cells. CD4+ and CD8+ T cells developed normally in Capn4(F/F:CD4-CRE mice and had severely diminished expression of Calpain 1 and 2, diminished talin proteolysis and impaired casein degradation. Calpain 4-deficient T cells showed no difference in adhesion or migration on the LFA-1 ligand ICAM-1 compared to control T cells. Moreover, there was no impairment in conjugation between Capn4(F/F:CD4-CRE T cells and antigen presenting cells, and the conjugates were still capable of polarizing LFA-1, PKC-theta and actin to the immune synapse. Furthermore, T cells from Capn4(F/F:CD4-CRE mice showed normal proliferation in response to either anti-CD3/CD28 coated beads or cognate antigen-loaded splenocytes. Finally, there were no differences in the rates of apoptosis following extrinsic and intrinsic apoptotic stimuli.Our findings demonstrate that calpain 4 is not necessary for LFA-1-mediated adhesion, conjugation or migration. These results challenge previous reports that implicate a central role for calpains in the regulation of T cell LFA-1 function.

  10. CD4+ T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4+ T cells to direct T helper 2 cell differentiation.

    Science.gov (United States)

    Khan, Mohd Moin; Chatterjee, Samit; Dwivedi, Ved Prakash; Pandey, Nishant Kumar; Singh, Yogesh; Tousif, Sultan; Bhavesh, Neel Sarovar; Van Kaer, Luc; Das, Jyoti; Das, Gobardhan

    2012-01-20

    The differentiation of naïve CD4(+) T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4(+) T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4(+) T cells. Induction of IL-4 in CD4(+) T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4(+) T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.

  11. The Efficiency of Delone Coverings of the Canonical Tilings MATH {cal T}(*(A_4)) -> T^*(A4) and MATH {cal T}(*(D_6)) -> T^*(D6)

    Science.gov (United States)

    Papadopolos, Zorka; Kasner, Gerald

    This chapter is devoted to the coverings of the two quasiperiodic canonical tilings MATH {cal T}(*(A_4)) -> T^*(A4) and MATH {cal T}(*(D_6)) equiv {cal T}(*(2F)) -> T^*(D6) T^*(2F), obtained by projection from the root lattices A4 and D6, respectively. In the first major part of this chapter, in Sect. 5.2, we shall introduce a Delone covering MATH {cal C}(s_{{cal) T}(*(A_4)}) -> C^sT^*(A4) of the 2-dimensional decagonal tiling MATH {cal T}(*(A_4)) -> T^*(A4). In the second major part of this chapter, Sect. 5.3, we summarize the results related to the Delone covering of the icosahedral tiling MATH {cal T}(*(D_6)) -> T^*(D6), MATH {cal C}_{{cal T}(*(D_6)}) -> CT^*(D6) and determine the zero-, single-, and double- deckings and the resulting thickness of the covering. In the conclusions section, we give some suggestions as to how the definition of the Delone covering might be changed in order to reach some real (full) covering of the icosahedral tiling MATH {cal T}(*(D_6)) -> T^*(D6). In Section 5.2 the definition of the Delone covering is also changed in order to avoid an unnecessary large thickness of the covering.

  12. A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations.

    Science.gov (United States)

    Vita, Roberto; Saraceno, Giovanna; Trimarchi, Francesco; Benvenga, Salvatore

    2013-02-01

    The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (L-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated L-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the L-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1-90, or with coffee ≤ 5 min later (improper habit, IH) on days 91-180. After 6 months, 2 patients volunteered for an acute loading test of 600 μg L-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06-0.16 mU/L (PH) versus 5.8-22.4 mU/L pre-switch (PH) and 0.025-0.29 mU/L (IH) versus 26-34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P coffee influenced L-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking L-T4.

  13. Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

    Science.gov (United States)

    Cobb, Dustin A.; Bhadra, Rajarshi

    2016-01-01

    CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

  14. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

    Science.gov (United States)

    Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

    2018-02-15

    The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Fabrication of 6FDA-durene membrane incorporated with zeolite T and aminosilane grafted zeolite T for CO2/CH4 separation

    Science.gov (United States)

    Jusoh, Norwahyu; Fong Yeong, Yin; Keong Lau, Kok; Shariff, Azmi Mohd

    2017-08-01

    In the present work, zeolite T and aminosilane grafted zeolite T are embedded into 6FDA-durene polyimide phase for the fabrication of mixed matrix membranes (MMMs). FESEM images demonstrated that the improvement of interfacial adhesion between zeolite and polymer phases in MMM loaded with aminosilane grafted zeolite T was not significant as compared to zeolite T/6FDA-durene MMM. From the gas permeation test, CO2/CH4 selectivity up to 26.4 was achieved using MMM containing aminosilane grafted zeolite T, while MMM loaded with ungrafted zeolite T showed CO2/CH4 selectivity of 19.1. In addition, MMM incorporated with aminosilane grafted zeolite T particles successfully lies on Robeson upper bound 2008, which makes it an attractive candidate for CO2/CH4 separation.

  16. N = (4,4 Supersymmetry and T-Duality

    Directory of Open Access Journals (Sweden)

    Malin Göteman

    2012-10-01

    Full Text Available A sigma model with four-dimensional target space parametrized by chiral and twisted chiral N =(2,2 superfields can be extended to N =(4,4 supersymmetry off-shell, but this is not true for a model of semichiral fields, where the N = (4,4 supersymmetry can only be realized on-shell. The two models can be related to each other by T-duality. In this paper we perform a duality transformation from a chiral and twisted chiral model with off-shell N = (4,4 supersymmetry to a semichiral model. We find that additional non-linear terms must be added to the original transformations to obtain a semichiral model with N =(4,4 supersymmetry, and that the algebra closes on-shell as a direct consequence of the T-duality.

  17. Cell-Intrinsic Roles for Autophagy in Modulating CD4 T Cell Functions

    Directory of Open Access Journals (Sweden)

    Elise Jacquin

    2018-05-01

    Full Text Available The catabolic process of autophagy plays important functions in inflammatory and immune responses by modulating innate immunity and adaptive immunity. Over the last decade, a cell-intrinsic role for autophagy in modulating CD4 T cell functions and differentiation was revealed. After the initial observation of autophagosomes in effector CD4 T cells, further work has shown that not only autophagy levels are modulated in CD4 T cells in response to environmental signals but also that autophagy critically affects the biology of these cells. Mouse models of autophagy deletion in CD4 T cells have indeed shown that autophagy is essential for CD4 T cell survival and homeostasis in peripheral lymphoid organs. Furthermore, autophagy is required for CD4 T cell proliferation and cytokine production in response to T cell receptor activation. Recent developments have uncovered that autophagy controls CD4 T cell differentiation and functions. While autophagy is required for the maintenance of immunosuppressive functions of regulatory T cells, it restrains the differentiation of TH9 effector cells, thus limiting their antitumor and pro-inflammatory properties. We will here discuss these findings that collectively suggest that therapeutic strategies targeting autophagy could be exploited for the treatment of cancer and inflammatory diseases.

  18. Linear Collider Physics Resource Book Snowmass 2001

    International Nuclear Information System (INIS)

    Ronan, M.T.

    2001-01-01

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e + e - linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e + e - linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e + e - linear collider; in any scenario that is now discussed, physics will benefit from the new information that e + e - experiments can provide. This last point merits further emphasis. If a new accelerator could be designed and built in a few years, it would make

  19. Linear Collider Physics Resource Book Snowmass 2001

    Energy Technology Data Exchange (ETDEWEB)

    Ronan (Editor), M.T.

    2001-06-01

    The American particle physics community can look forward to a well-conceived and vital program of experimentation for the next ten years, using both colliders and fixed target beams to study a wide variety of pressing questions. Beyond 2010, these programs will be reaching the end of their expected lives. The CERN LHC will provide an experimental program of the first importance. But beyond the LHC, the American community needs a coherent plan. The Snowmass 2001 Workshop and the deliberations of the HEPAP subpanel offer a rare opportunity to engage the full community in planning our future for the next decade or more. A major accelerator project requires a decade from the beginning of an engineering design to the receipt of the first data. So it is now time to decide whether to begin a new accelerator project that will operate in the years soon after 2010. We believe that the world high-energy physics community needs such a project. With the great promise of discovery in physics at the next energy scale, and with the opportunity for the uncovering of profound insights, we cannot allow our field to contract to a single experimental program at a single laboratory in the world. We believe that an e{sup +}e{sup -} linear collider is an excellent choice for the next major project in high-energy physics. Applying experimental techniques very different from those used at hadron colliders, an e{sup +}e{sup -} linear collider will allow us to build on the discoveries made at the Tevatron and the LHC, and to add a level of precision and clarity that will be necessary to understand the physics of the next energy scale. It is not necessary to anticipate specific results from the hadron collider programs to argue for constructing an e{sup +}e{sup -} linear collider; in any scenario that is now discussed, physics will benefit from the new information that e{sup +}e{sup -} experiments can provide. This last point merits further emphasis. If a new accelerator could be designed and

  20. Preparation of quality control samples for its use in the radioimmunoassay de T3, T4 and TSH

    International Nuclear Information System (INIS)

    Lavalley E, C.; Delgado S, B.; Ruiz J, A.; Zambrano A, F.

    1991-09-01

    The use of quality control samples is necessary to evaluate, in a very simple way, the quality of the assays in the radioimmunoanalysis, since allows to settle down a quality control intra and inter analysis. In this work the methodology used for the preparation of these samples with low, media and high concentration for hormones related with the thyroid is shown, being obtained the following concentrations: 50, 200 and 500 ng/dl for T 3 ; 5.6, 7.8 and 14.4 μ g/dl for T 4 and 5.4, 13.4 and >50 μ U I/ml for TSH. (Author)

  1. Ku to V-band 4-bit MEMS phase shifter bank using high isolation SP4T switches and DMTL structures

    Science.gov (United States)

    Dey, Sukomal; Koul, Shiban K.; Poddar, Ajay K.; Rohde, Ulrich L.

    2017-10-01

    This work presents a micro-electro-mechanical system (MEMS) based on a wide-band 4-bit phase shifter using two back-to-back single-pole-four-throw (SP4T) switches and four different distributed MEMS transmission line (DMTL) structures that are implemented on 635 µm alumina substrate using surface micromachining process. An SP4T switch is designed with a series-shunt configuration and it demonstrates an average return loss of  >17 dB, an insertion loss of  28 dB up to 60 GHz. A maximum area of the SP4T switch is ~0.76 mm2. Single-pole-single-throw and SP4T switches are capable of handling 1 W of radio frequency (RF) power up to  >100 million cycles at 25° C; they can even sustained up to  >70 million cycles with 1 W at 85 °C. The proposed wide-band phase shifter works at 17 GHz (Ku-band), 25 GHz (K-band), 35 GHz (Ka-band) and 60 GHz (V-band) frequencies. Finally,a 4-bit phase shifter demonstrates an average insertion loss of  10 dB and maximum phase error of ~3.8° at 60 GHz frequency over 500 MHz bandwidth. Total area of the fabricated device is ~11 mm2. In addition, the proposed device works well up to  >107 cycles with 1 W of RF power. To the best of the author’s knowledge, this is the best reported wide-band MEMS 4-bit phase shifter in the literature that works with a constant resolution.

  2. Proceedings of the 1996 DPF/DPB Summer Study on New Directions in High-energy Physics (Snowmass 96)

    International Nuclear Information System (INIS)

    Weyhrauch, Y.

    2004-01-01

    Production of the Proceedings of the 1996 DPB/DPF Summer Study in High-Energy Physics built on the methods, lessons, and technology of the production process used for the Proceedings of the 1995 Particle Accelerator Conference (PAC95). For PAC95, authors were asked to submit PostScript, source files, and hard copy. Producing the proceedings took 16 months of official FTE in addition to countless hours of volunteer work by two additional people--the entire production process was accomplished in just under 9 months. In that time, the PAC95 production team quality checked every file (1099 submissions, totaling 3429 pages) and rebuilt about two thirds of them to fix problems with fonts and figures, and various other problems. Needless to say, this was an expensive process. The Snowmass proceedings project started with a much smaller budget and a shorter production schedule, resulting in a much more ambitious plan. The goal was, as for PAC95, to produce both a paper and a CD version of the proceedings. This time, the goal was to complete the project in only 6 months, using half of a staff person from the SLAC Technical Publications Department (responsible for technical design and implementation as well as project management), along with 6 months of a full-time temporary employee to answer the phone and coordinate author support. The conference editors and I decided on a strategy using the World Wide Web for submission and quality assurance testing. The resulting procedure allowed authors to check the quality of their own PDF files, prevented random browsing of papers before publication of the proceedings, and required minimal human intervention (though we easily could have used a few more bodies manning the help lines). To this end, we set up a Power Macintosh running FileMaker Pro 3.0 (a relational database application), WebSTAR (Macintosh Web server software), WEB/FM (CGI package for FileMaker Pro/ WebSTAR interface), and NetPresenz (Macintosh ftp server) and created

  3. Combination L-T3 and L-T4 therapy for hypothyroidism.

    Science.gov (United States)

    Wartofsky, Leonard

    2013-10-01

    Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

  4. The Impact of Sex Work Interruption on Blood-Derived T Cells in Sex Workers from Nairobi, Kenya.

    Science.gov (United States)

    Omollo, Kenneth; Boily-Larouche, Geneviève; Lajoie, Julie; Kimani, Makobu; Cheruiyot, Julianna; Kimani, Joshua; Oyugi, Julius; Fowke, Keith Raymond

    Unprotected sexual intercourse exposes the female genital tract (FGT) to semen-derived antigens, which leads to a proinflammatory response. Studies have shown that this postcoital inflammatory response can lead to recruitment of activated T cells to the FGT, thereby increasing risk of HIV infection. The purpose of this study was to evaluate the impact of sex work on activation and memory phenotypes of peripheral T cells among female sex workers (FSW) from Nairobi, Kenya. Thirty FSW were recruited from the Pumwani Sex Workers Cohort, 10 in each of the following groups: HIV-exposed seronegative (at least 7 years in active sex work), HIV positive, and New Negative (HIV negative, less than 3 years in active sex work). Blood was obtained at three different phases (active sex work, abstinence from sex work-sex break, and following resumption of sex work). Peripheral blood mononuclear cells were isolated and stained for phenotypic markers (CD3, CD4, CD8, and CD161), memory phenotype markers (CD45RA and CCR7), activation markers (CD69, HLA-DR, and CD95), and the HIV coreceptor (CCR5). T-cell populations were compared between groups. In HIV-positive women, CD8+CCR5+ T cells declined at the sex break period, while CD4+CD161+ T cells increased when returning to sex work. All groups showed no significant changes in systemic T-cell activation markers following the interruption of sex work, however, significant reductions in naive CD8+ T cells were noted. For each of the study points, HIV positives had higher effector memory and CD8+CD95+ T cells and lower naive CD8+ T cells than the HIV-uninfected groups. Interruption of sex work had subtle effects on systemic T-cell memory phenotypes.

  5. Memory T follicular helper CD4 T cells

    Directory of Open Access Journals (Sweden)

    J. Scott eHale

    2015-02-01

    Full Text Available T follicular helper (Tfh cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses. Until recently, it remained unclear whether Tfh cells differentiated into memory cells and whether they maintain their Tfh commitment at the memory phase. This review will highlight several recent studies that support the idea of Tfh-committed CD4 T cells at the memory stage of the immune response. The implication of these findings is that memory Tfh cells retain their capacity to recall their Tfh-specific effector functions upon reactivation to provide help for B cell responses and play an important role in prime and boost vaccination or during recall responses to infection. The markers that are useful for distinguishing Tfh effector and memory cells, as well as the limitations of using these markers will be discussed. Tfh effector and memory generation, lineage maintenance, and plasticity relative to other T helper lineages (Th1, Th2, Th17, etc will also be discussed. Ongoing discoveries regarding the maintenance and lineage stability versus plasticity of memory Tfh cells will improve strategies that utilize CD4 T cell memory to modulate antibody responses during prime and boost vaccination.

  6. Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

    Science.gov (United States)

    Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

    2015-01-01

    ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are

  7. Working Group Report: Lattice Field Theory

    Energy Technology Data Exchange (ETDEWEB)

    Blum, T.; et al.,

    2013-10-22

    This is the report of the Computing Frontier working group on Lattice Field Theory prepared for the proceedings of the 2013 Community Summer Study ("Snowmass"). We present the future computing needs and plans of the U.S. lattice gauge theory community and argue that continued support of the U.S. (and worldwide) lattice-QCD effort is essential to fully capitalize on the enormous investment in the high-energy physics experimental program. We first summarize the dramatic progress of numerical lattice-QCD simulations in the past decade, with some emphasis on calculations carried out under the auspices of the U.S. Lattice-QCD Collaboration, and describe a broad program of lattice-QCD calculations that will be relevant for future experiments at the intensity and energy frontiers. We then present details of the computational hardware and software resources needed to undertake these calculations.

  8. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-01-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

  9. Quality control of radioimmunoassay reagents for T4

    International Nuclear Information System (INIS)

    Wayan Radiatning, S.

    1987-01-01

    Quality control of radioimmunoassay reagents for T4. A program of quality control testing has been carried out for 125 I-T4, T4 standards and T4 antisera. 125 I-labelled T4 has been tested for its specific activity, radiochemical purity using a Sephadex G-25 column, immunological activity, based on the immunological reaction between labelled antigen and excess T4 antibody, and non-specific binding. The useful shelf-life of the labelled compound was determined by monitoring the decrease in radiochemical purity and immunological activity, and the increase in non-specific binding. T4 standards were calibrated by means of T4 RIA kit manufactured by DPC (Diagnostic Products Corporation). A test on parallelism was also performed using hyperthyroid sera. T4 antisera were evaluated with respect to titre, avidity and specifity. The test results on 125 I-T4 show a specific activity varying between 1830-2020 uCi/ug, a radiochemical purity above 90%, an immunological more than 80% and a non-specific binding of less than 5%. The standard curve for T4 was found to coincide well with the standard curve of the DPC kit and parallel with the curve for hyperthyroid sera. The titre of T4 antisera obtained was 1:300, the avidity was about 4.8 x 10 7 and the cross-reaction for T3 was 1.6%. It can be concluded from the experimental results, that the 125 I-T4, T4 standards and T4 antisera prepared meet the requirements for the manufacture of T4 kits. (author). 5 refs.; 14 figs

  10. T4 thyrotoxicosis: an independent disease or the effect of an alteration in the peripheral metabolism of T4

    International Nuclear Information System (INIS)

    Maciel, R.M.B.; Vieira, J.G.H.; Russo, E.M.K.; Dib, S.A.

    1983-01-01

    Six cases of T 4 thyrotoxicosis were observed in 250 patients with hyperthyroidism. In the 6 episodes, the thyrotoxicosis was associated with severe systemic illness or with the admnistration of propanolol, which blocked the peripheral convertion of T 4 to T 3 . These data indicate that T 4 thyrotoxicosis reflects an alteration in the peripheral metabolism of T 4 produced by systemic illness or drugs. (M.A.C.) [pt

  11. On 4-critical t-perfect graphs

    OpenAIRE

    Benchetrit, Yohann

    2016-01-01

    It is an open question whether the chromatic number of $t$-perfect graphs is bounded by a constant. The largest known value for this parameter is 4, and the only example of a 4-critical $t$-perfect graph, due to Laurent and Seymour, is the complement of the line graph of the prism $\\Pi$ (a graph is 4-critical if it has chromatic number 4 and all its proper induced subgraphs are 3-colorable). In this paper, we show a new example of a 4-critical $t$-perfect graph: the complement of the line gra...

  12. Preparation of quality control samples for its use in the radioimmunoassay de T{sub 3}, T{sub 4} and TSH; Preparacion de muestras de control de calidad para su uso en el radioinmunoanalisis de T{sub 3}, T{sub 4} y TSH

    Energy Technology Data Exchange (ETDEWEB)

    Lavalley E, C; Delgado S, B; Ruiz J, A; Zambrano A, F

    1991-09-15

    The use of quality control samples is necessary to evaluate, in a very simple way, the quality of the assays in the radioimmunoanalysis, since allows to settle down a quality control intra and inter analysis. In this work the methodology used for the preparation of these samples with low, media and high concentration for hormones related with the thyroid is shown, being obtained the following concentrations: 50, 200 and 500 ng/dl for T{sub 3}; 5.6, 7.8 and 14.4 {mu} g/dl for T{sub 4} and 5.4, 13.4 and >50 {mu} U I/ml for TSH. (Author)

  13. Synthesis and structure of the extended phosphazane ligand [(1,4-C6H4){N(μ-PN(t)Bu)2N(t)Bu}2](4).

    Science.gov (United States)

    Sevilla, Raquel; Less, Robert J; García-Rodríguez, Raúl; Bond, Andrew D; Wright, Dominic S

    2016-02-07

    The reaction of the phenylene-bridged precursor (1,4-C6H4)[N(PCl2)2]2 with (t)BuNH2 in the presence of Et3N gives the new ligand precursor (1,4-C6H4)[N(μ-N(t)Bu)2(PNH(t)Bu)2]2, deprotonation of which with Bu2Mg gives the novel tetraanion [(1,4-C6H4){N(μ-N(t)Bu)2(PN(t)Bu)2}2](4-).

  14. Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-09-06

    CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

  15. Comparison of Immunoassay methods for T3, T4 and TSH

    International Nuclear Information System (INIS)

    Alonso Rodríguez, Celia A.

    2016-01-01

    Measurements of T3, T4 and TSH have been considered very important in the diagnosis and monitoring of thyroid diseases both overt and subclinical. These subclinical diseases are actively seeking for years, both in healthy patients and hospitalized for other illnesses; and in the population over 35 years, especially women, in health checkups. The active search for these diseases requires the use of rapid and reliable techniques; that can be developed massively, with good level of detectability and comparable. The overall objective is to present the evaluation of different immunoassay techniques with respect to the RIA and IRMA: ELISA, chemiluminescence, Amplified Chemiluminescence, electrochemiluminescence Immunofluorescence. Compare including automatic methods and analyze the cost and feasibility of them for laboratory immunoassay. ELISA colorimetric technique for dosing was comparable to RIA T4, not for T3. Chemiluminescence (AMERLITE) compared to dosing RIA and IRMA T4 to TSH proved to be valid for both. Amplified Chemiluminescence (Immulite) compared to IRMA for TSH was no significant difference. Electrochemiluminescence (Elecsys 2010) compared to T3 and T4 RIA and IRMA for TSH, no significant differences for T4 and TSH; but no variation to T3. Immunofluorescence (AIA-600) used to compare with RIA for T3 and T4, and TSH IRMA, no significant differences for the measured analytes. Benchmarking of automatic methods suggests that the most thrifty of trials is Immunofluorescence the AIA-600, regarding calibration and control, programming time, randomization and the ability to save the value of the fluorescence deferred calculations for tests without valid at the time of realizing calibration. Analyzing the cost and feasibility of these methods for laboratory immunoassay, we must consider that their characteristics electrochemiluminescence is the fastest, but its price is prohibitive for our health systems. The AIA-600 appears to be the method of choice for its

  16. Effects of potassium iodide in concentrations of TSH, tT3 and tT4 in serum of subjects with sporotrichosis.

    Science.gov (United States)

    Ramírez Soto, Max Carlos

    2014-08-01

    The saturated potassium iodide solution (SSKI) as treatment for sporotrichosis may cause hypothyroidism by suppressing the synthesis of thyroid hormones (tT3 and tT4 ) and the iodine excess could lead to thyrotoxicosis. Evaluating the changes in serum levels of TSH, tT3 and tT4 in euthyroid patients with sporotrichosis treated with SSKI. For the selection of euthyroid patients, TSH, tT3 and tT4 concentrations were measured for those adults and children diagnosed with sporotrichosis. Each paediatric patient was administered SSKI orally in increasing doses of 2-20 drops/3 times/day and 4-40 drops/3 times/day in adults. Serum concentrations of TSH, tT3 and tT4 were measured 20 days after started the treatment and 15 days posttreatment. Eight euthyroid patients aged between 2 to 65 years old were included. After 20 days of treatment, two suffered subclinical hypothyroidism, one developed subclinical hyperthyroidism, and one hyperthyroxinaemia euthyroid. At 15 days posttreatment only four patients were evaluated and all serum levels of TSH, tT3 and tT4 were normal. Some euthyroid patients with sporotrichosis can develop hyperthyroidism or subclinical iodine-induced hypothyroidism, during the administration of 3 or 6 g SSKI/day. © 2014 Blackwell Verlag GmbH.

  17. Comparative studies of commercially available T4-RIA-kits. Pt. 2

    International Nuclear Information System (INIS)

    Schmidt, H.A.E.; Lipke, P.

    1978-01-01

    The investigation of the tested commercially available T 4 -RIA-Kits have shown that: The separation of hypo-, eu- and hyperthyroid values is better with kits a) and f) than with b), c), d) and e), though all kits give acceptable values under routine operating conditions, kit b) takes less time and work than the other tested kits, depending on the kit used, the time needed for 100 determinations varies between 1,5 and 4 hr. A general recommendation for one of the tested T 4 -RIA-Kits cannot be made since the choice of a kit depends not only on the criteria discussed but also on local circumstances. (orig.) [de

  18. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Directory of Open Access Journals (Sweden)

    Hui Xu

    2010-11-01

    Full Text Available MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  19. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Science.gov (United States)

    Xu, Hui; Yan, Yaping; Williams, Mark S; Carey, Gregory B; Yang, Jingxian; Li, Hongmei; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2010-11-01

    MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  20. Structural, Electronic, and Thermodynamic Properties of Tetragonal t-SixGe3−xN4

    Directory of Open Access Journals (Sweden)

    Chenxi Han

    2018-03-01

    Full Text Available The structural, mechanical, anisotropic, electronic, and thermal properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 in the tetragonal phase are systematically investigated in the present work. The mechanical stability is proved by the elastic constants of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4. Moreover, they all demonstrate brittleness, because B/G < 1.75, and v < 0.26. The elastic anisotropy of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 is characterized by Poisson’s ratio, Young’s modulus, the percentage of elastic anisotropy for bulk modulus AB, the percentage of elastic anisotropy for shear modulus AG, and the universal anisotropic index AU. The electronic structures of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are all wide band gap semiconductor materials, with band gaps of 4.26 eV, 3.94 eV, 3.83 eV, and 3.25 eV, respectively, when using the Heyd-Scuseria-Ernzerhof (HSE06 hybrid functional. Moreover, t-Ge3N4 is a quasi-direct gap semiconductor material. The thermodynamic properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are investigated utilizing the quasi-harmonic Debye model. The effects of temperature and pressure on the thermal expansion coefficient, heat capacity, Debye temperature, and Grüneisen parameters are discussed in detail.

  1. AtlasT4SS: a curated database for type IV secretion systems.

    Science.gov (United States)

    Souza, Rangel C; del Rosario Quispe Saji, Guadalupe; Costa, Maiana O C; Netto, Diogo S; Lima, Nicholas C B; Klein, Cecília C; Vasconcelos, Ana Tereza R; Nicolás, Marisa F

    2012-08-09

    The type IV secretion system (T4SS) can be classified as a large family of macromolecule transporter systems, divided into three recognized sub-families, according to the well-known functions. The major sub-family is the conjugation system, which allows transfer of genetic material, such as a nucleoprotein, via cell contact among bacteria. Also, the conjugation system can transfer genetic material from bacteria to eukaryotic cells; such is the case with the T-DNA transfer of Agrobacterium tumefaciens to host plant cells. The system of effector protein transport constitutes the second sub-family, and the third one corresponds to the DNA uptake/release system. Genome analyses have revealed numerous T4SS in Bacteria and Archaea. The purpose of this work was to organize, classify, and integrate the T4SS data into a single database, called AtlasT4SS - the first public database devoted exclusively to this prokaryotic secretion system. The AtlasT4SS is a manual curated database that describes a large number of proteins related to the type IV secretion system reported so far in Gram-negative and Gram-positive bacteria, as well as in Archaea. The database was created using the RDBMS MySQL and the Catalyst Framework based in the Perl programming language and using the Model-View-Controller (MVC) design pattern for Web. The current version holds a comprehensive collection of 1,617 T4SS proteins from 58 Bacteria (49 Gram-negative and 9 Gram-Positive), one Archaea and 11 plasmids. By applying the bi-directional best hit (BBH) relationship in pairwise genome comparison, it was possible to obtain a core set of 134 clusters of orthologous genes encoding T4SS proteins. In our database we present one way of classifying orthologous groups of T4SSs in a hierarchical classification scheme with three levels. The first level comprises four classes that are based on the organization of genetic determinants, shared homologies, and evolutionary relationships: (i) F-T4SS, (ii) P-T4SS, (iii

  2. Tools-4-Metatool (T4M): online suite of web-tools to process stoichiometric network analysis data from Metatool.

    Science.gov (United States)

    Xavier, Daniela; Vázquez, Sara; Higuera, Clara; Morán, Federico; Montero, Francisco

    2011-08-01

    Tools-4-Metatool (T4M) is a suite of web-tools, implemented in PERL, which analyses, parses, and manipulates files related to Metatool. Its main goal is to assist the work with Metatool. T4M has two major sets of tools: Analysis and Compare. Analysis visualizes the results of Metatool (convex basis, elementary flux modes, and enzyme subsets) and facilitates the study of metabolic networks. It is composed of five tools: MDigraph, MetaMatrix, CBGraph, EMGraph, and SortEM. Compare was developed to compare different Metatool results from different networks. This set consists of: Compara and ComparaSub which compare network subsets providing outputs in different formats and ComparaEM that seeks for identical elementary modes in two metabolic networks. The suite T4M also includes one script that generates Metatool input: CBasis2Metatool, based on a Metatool output file that is filtered by a list of convex basis' metabolites. Finally, the utility CheckMIn checks the consistency of the Metatool input file. T4M is available at http://solea.quim.ucm.es/t4m. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Longitudinal tDCS: Consistency across Working Memory Training Studies

    Directory of Open Access Journals (Sweden)

    Marian E. Berryhill

    2017-04-01

    Full Text Available There is great interest in enhancing and maintaining cognitive function. In recent years, advances in noninvasive brain stimulation devices, such as transcranial direct current stimulation (tDCS, have targeted working memory in particular. Despite controversy surrounding outcomes of single-session studies, a growing field of working memory training studies incorporate multiple sessions of tDCS. It is useful to take stock of these findings because there is a diversity of paradigms employed and the outcomes observed between research groups. This will be important in assessing cognitive training programs paired with stimulation techniques and identifying the more useful and less effective approaches. Here, we treat the tDCS+ working memory training field as a case example, but also survey training benefits in other neuromodulatory techniques (e.g., tRNS, tACS. There are challenges associated with the broad parameter space including: individual differences, stimulation intensity, duration, montage, session number, session spacing, training task selection, timing of follow up testing, near and far transfer tasks. In summary, although the field of assisted cognitive training is young, some design choices are more favorable than others. By way of heuristic, the current evidence supports including more training/tDCS sessions (5+, applying anodal tDCS targeting prefrontal regions, including follow up testing on trained and transfer tasks after a period of no contact. What remains unclear, but important for future translational value is continuing work to pinpoint optimal values for the tDCS parameters on a per cognitive task basis. Importantly the emerging literature shows notable consistency in the application of tDCS for WM across various participant populations compared to single session experimental designs.

  4. Report of the working group on detector simulation

    International Nuclear Information System (INIS)

    Price, L.E.; Lebrun, P.

    1986-01-01

    An ad hoc group at Snowmass reviewed the need for detector simulation to support detectors at the SSC. This report first reviews currently available programs for detector simulation, both those written for single specific detectors and those aimed at general utility. It then considers the requirements for detector simulation for the SSC, with particular attention to enhancements that are needed relative to present programs. Finally, a list of recommendations is given

  5. CD4+ T cell effects on CD8+ T cell location defined using bioluminescence.

    Directory of Open Access Journals (Sweden)

    Mitra Azadniv

    2011-01-01

    Full Text Available T lymphocytes of the CD8+ class are critical in delivering cytotoxic function and in controlling viral and intracellular infections. These cells are "helped" by T lymphocytes of the CD4+ class, which facilitate their activation, clonal expansion, full differentiation and the persistence of memory. In this study we investigated the impact of CD4+ T cells on the location of CD8+ T cells, using antibody-mediated CD4+ T cell depletion and imaging the antigen-driven redistribution of bioluminescent CD8+ T cells in living mice. We documented that CD4+ T cells influence the biodistribution of CD8+ T cells, favoring their localization to abdominal lymph nodes. Flow cytometric analysis revealed that this was associated with an increase in the expression of specific integrins. The presence of CD4+ T cells at the time of initial CD8+ T cell activation also influences their biodistribution in the memory phase. Based on these results, we propose the model that one of the functions of CD4+ T cell "help" is to program the homing potential of CD8+ T cells.

  6. Collaborative Working Architecture for IoT-Based Applications.

    Science.gov (United States)

    Mora, Higinio; Signes-Pont, María Teresa; Gil, David; Johnsson, Magnus

    2018-05-23

    The new sensing applications need enhanced computing capabilities to handle the requirements of complex and huge data processing. The Internet of Things (IoT) concept brings processing and communication features to devices. In addition, the Cloud Computing paradigm provides resources and infrastructures for performing the computations and outsourcing the work from the IoT devices. This scenario opens new opportunities for designing advanced IoT-based applications, however, there is still much research to be done to properly gear all the systems for working together. This work proposes a collaborative model and an architecture to take advantage of the available computing resources. The resulting architecture involves a novel network design with different levels which combines sensing and processing capabilities based on the Mobile Cloud Computing (MCC) paradigm. An experiment is included to demonstrate that this approach can be used in diverse real applications. The results show the flexibility of the architecture to perform complex computational tasks of advanced applications.

  7. t4 Workshop Report

    Science.gov (United States)

    Silbergeld, Ellen K.; Contreras, Elizabeth Q.; Hartung, Thomas; Hirsch, Cordula; Hogberg, Helena; Jachak, Ashish C.; Jordan, William; Landsiedel, Robert; Morris, Jeffery; Patri, Anil; Pounds, Joel G.; de Vizcaya Ruiz, Andrea; Shvedova, Anna; Tanguay, Robert; Tatarazako, Norihasa; van Vliet, Erwin; Walker, Nigel J.; Wiesner, Mark; Wilcox, Neil; Zurlo, Joanne

    2014-01-01

    Summary In October 2010, a group of experts met as part of the transatlantic think tank for toxicology (t4) to exchange ideas about the current status and future of safety testing of nanomaterials. At present, there is no widely accepted path forward to assure appropriate and effective hazard identification for engineered nanomaterials. The group discussed needs for characterization of nanomaterials and identified testing protocols that incorporate the use of innovative alternative whole models such as zebrafish or C. elegans, as well as in vitro or alternative methods to examine specific functional pathways and modes of action. The group proposed elements of a potential testing scheme for nanomaterials that works towards an integrated testing strategy, incorporating the goals of the NRC report Toxicity Testing in the 21st Century: A Vision and a Strategy by focusing on pathways of toxic response, and utilizing an evidence-based strategy for developing the knowledge base for safety assessment. Finally, the group recommended that a reliable, open, curated database be developed that interfaces with existing databases to enable sharing of information. PMID:21993959

  8. t4 Workshop Report*

    Science.gov (United States)

    Kleensang, Andre; Maertens, Alexandra; Rosenberg, Michael; Fitzpatrick, Suzanne; Lamb, Justin; Auerbach, Scott; Brennan, Richard; Crofton, Kevin M.; Gordon, Ben; Fornace, Albert J.; Gaido, Kevin; Gerhold, David; Haw, Robin; Henney, Adriano; Ma’ayan, Avi; McBride, Mary; Monti, Stefano; Ochs, Michael F.; Pandey, Akhilesh; Sharan, Roded; Stierum, Rob; Tugendreich, Stuart; Willett, Catherine; Wittwehr, Clemens; Xia, Jianguo; Patton, Geoffrey W.; Arvidson, Kirk; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Adeleye, Yeyejide; Kanehisa, Minoru; Carmichael, Paul; Andersen, Melvin E.; Hartung, Thomas

    2014-01-01

    Summary Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation – the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as “A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants”. It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities. PMID:24127042

  9. CD4+/CD8+ double-positive T cells

    DEFF Research Database (Denmark)

    Overgaard, Nana H; Jung, Ji-Won; Steptoe, Raymond J

    2015-01-01

    CD4(+)/CD8(+) DP thymocytes are a well-described T cell developmental stage within the thymus. However, once differentiated, the CD4(+) lineage or the CD8(+) lineage is generally considered to be fixed. Nevertheless, mature CD4(+)/CD8(+) DP T cells have been described in the blood and peripheral...... cells, CD4(+)/CD8(+) T cell populations, outside of the thymus, have recently been described to express concurrently ThPOK and Runx3. Considerable heterogeneity exists within the CD4(+)/CD8(+) DP T cell pool, and the function of CD4(+)/CD8(+) T cell populations remains controversial, with conflicting...... reports describing cytotoxic or suppressive roles for these cells. In this review, we describe how transcriptional regulation, lineage of origin, heterogeneity of CD4 and CD8 expression, age, species, and specific disease settings influence the functionality of this rarely studied T cell population....

  10. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

    Science.gov (United States)

    Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

    2016-01-01

    Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

  11. Development and characterization of radioimmunoassay methods for the measurement of iodothyronines (T4, T3 and rT3)

    International Nuclear Information System (INIS)

    Russo, E.M.K.; Vieira, J.G.H.; Barros Maciel, R.M. de; Fonseca, R.M.G.

    1982-01-01

    The experience acquired in the development of radioimmunoassay for T 4 , T 3 and rT 3 in unextrated serum is described. Antisera were produced in rabbits using iodothyronines conjugated to bovine serum albumin: the antisera selected provided the development of sensitive and specific radioassay methods. Stable high activity T 3 , T 4 and rT 3 tracers were prepared by iodination of 3,5 T 2 , T 3 and 3,3' T 2 by the chloramine-T method, and purified by column chromatography on Sephadex G25. Binding of those iodothyronines to endogenous serum proteins was blocked by including 8-aniline-1-naphtalene sulphonic acid (ANSA) in the T 4 and T 3 assays and thymerosal in the rT 3 assay. Normal values were defined in 46 healthy euthyroid adults of both sexes: T 4 = 7,1 +- 1,3μg/dl; T 3 = 139 +- 35ng/dl and rT 3 = 18,0 +- 7,9ng/dl. (Author) [pt

  12. Summary of the particle physics and technology working group

    International Nuclear Information System (INIS)

    Stephan Lammel et al. email = crathbun@fnal.gov

    2002-01-01

    Progress in particle physics has been tightly related to technological advances during the past half century. Progress in technologies has been driven in many cases by the needs of particle physics. Often, these advances have benefited fields beyond particle physics: other scientific fields, medicine, industrial development, and even found commercial applications. The particle physics and technology working group of Snowmass 2001 reviewed leading-edge technologies recently developed or in the need of development for particle physics. The group has identified key areas where technological advances are vital for progress in the field, areas of opportunities where particle physics may play a principle role in fostering progress, and areas where advances in other fields may directly benefit particle physics. The group has also surveyed the technologies specifically developed or enhanced by research in particle physics that benefit other fields and/or society at large

  13. Reactive Oxygen Species and Their Implications on CD4+ T Cells in Type 1 Diabetes.

    Science.gov (United States)

    Previte, Dana M; Piganelli, Jon D

    2017-11-28

    Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4 + T cell activation and differentiation. As CD4 + T cells are a significant contributor to pancreatic β cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4 + T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and β cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4 + T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4 + T cells have been done to examine the influence of redox on CD4 + T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4 + T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4 + T cell formation and function. Antioxid. Redox Signal. 00, 000-000.

  14. Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4"

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E

    1990-01-01

    Recent studies of cellular T4 and T3 uptake have indicated active transport of the hormones into the cell rather than passive diffusion of the non-protein bound fraction. In order to study the significance of the extracellular environment, oxygen consumption and glucose uptake were examined...... in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen......-consumption in a dose dependent manner but the T4 stimulation was dependent on the total concentration of T4 and did not differ between serum incubation or non-protein containing medium. Addition of ANS (100 mg/l) which inhibits binding of T4 to TBG, did not increase T4 effect in serum. Inhibition of the Na...

  15. Cytotoxic human CD4(+) T cells

    NARCIS (Netherlands)

    van de Berg, Pablo J.; van Leeuwen, Ester M.; ten Berge, Ineke J.; van Lier, Rene

    2008-01-01

    The induction of adaptive immune responses critically depends on helper signals provided by CD4(+) T cells. These signals not only license antigen presenting cells (APC) to activate naïve CD8(+) T cells leading to the formation of vast numbers of cytotoxic T lymphocytes but also support the

  16. Genetic diversity among five T4-like bacteriophages

    Directory of Open Access Journals (Sweden)

    Bertrand Claire

    2006-05-01

    Full Text Available Abstract Background Bacteriophages are an important repository of genetic diversity. As one of the major constituents of terrestrial biomass, they exert profound effects on the earth's ecology and microbial evolution by mediating horizontal gene transfer between bacteria and controlling their growth. Only limited genomic sequence data are currently available for phages but even this reveals an overwhelming diversity in their gene sequences and genomes. The contribution of the T4-like phages to this overall phage diversity is difficult to assess, since only a few examples of complete genome sequence exist for these phages. Our analysis of five T4-like genomes represents half of the known T4-like genomes in GenBank. Results Here, we have examined in detail the genetic diversity of the genomes of five relatives of bacteriophage T4: the Escherichia coli phages RB43, RB49 and RB69, the Aeromonas salmonicida phage 44RR2.8t (or 44RR and the Aeromonas hydrophila phage Aeh1. Our data define a core set of conserved genes common to these genomes as well as hundreds of additional open reading frames (ORFs that are nonconserved. Although some of these ORFs resemble known genes from bacterial hosts or other phages, most show no significant similarity to any known sequence in the databases. The five genomes analyzed here all have similarities in gene regulation to T4. Sequence motifs resembling T4 early and late consensus promoters were observed in all five genomes. In contrast, only two of these genomes, RB69 and 44RR, showed similarities to T4 middle-mode promoter sequences and to the T4 motA gene product required for their recognition. In addition, we observed that each phage differed in the number and assortment of putative genes encoding host-like metabolic enzymes, tRNA species, and homing endonucleases. Conclusion Our observations suggest that evolution of the T4-like phages has drawn on a highly diverged pool of genes in the microbial world. The T4

  17. Rapid T4 radioimmunoassay with antibody of Czechoslovak production

    Energy Technology Data Exchange (ETDEWEB)

    Cechacek, Z [MUNZ, Brno (Czechoslovakia) Div. of Nuclear Nedicine

    1978-06-30

    Rapid T4-RIA based on the T4-antibody produced in Institute of Experimental Endocrinology in Bratislava is described. The used T4-antibody was found as suitable preparation for the routine T4-RIA and is comparable to the foreign materials. T4 antibody was obtained by rabbit immunization and supplied as antiserum in a frozen state. It was properly diluted with 0.08M barbital buffer, pH 8.6, containing 0.a5% sodium ethylmercurythiosalicylate and 0.5% BSA.

  18. Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

    Science.gov (United States)

    Zhang, Mingce; Robinson, Tanya O; Duverger, Alexandra; Kutsch, Olaf; Heath, Sonya L; Cron, Randy Q

    2018-03-01

    During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into CD4+ FoxP3+ T regulatory cells by production of IFN-γ.

    Directory of Open Access Journals (Sweden)

    Shravan Madireddi

    Full Text Available Tumors convert conventional CD4(+ T cells into induced CD4(+CD25(+FoxP3(+ T regulatory (iTreg cells that serve as an effective means of immune evasion. Therefore, the blockade of conventional CD4(+ T cell conversion into iTreg cells represents an attractive target for improving the efficacy of various immunotherapeutic approaches. Using a novel form of 4-1BBL molecule, SA-4-1BBL, we previously demonstrated that costimulation via 4-1BB receptor renders both CD4(+and CD8(+ T effector (Teff cells refractory to inhibition by Treg cells and increased intratumoral Teff/Treg cell ratio that correlated with therapeutic efficacy in various preclinical tumor models. Building on these studies, we herein show for the first time, to our knowledge, that signaling through 4-1BB inhibits antigen- and TGF-β-driven conversion of naïve CD4(+FoxP3(- T cells into iTreg cells via stimulation of IFN-γ production by CD4(+FoxP3(- T cells. Importantly, treatment with SA-4-1BBL blocked the conversion of CD4(+FoxP3(- T cells into Treg cells by EG.7 tumors. Taken together with our previous studies, these results show that 4-1BB signaling negatively modulate Treg cells by two distinct mechanisms: i inhibiting the conversion of CD4(+FoxP3(- T cells into iTreg cells and ii endowing Teff cells refractory to inhibition by Treg cells. Given the dominant role of Treg cells in tumor immune evasion mechanisms, 4-1BB signaling represents an attractive target for favorably tipping the Teff:Treg balance toward Teff cells with important implications for cancer immunotherapy.

  20. When Evidence Doesn’t Work (Editorial

    Directory of Open Access Journals (Sweden)

    Lindsay Glynn

    2007-12-01

    Full Text Available I was listening intently to a discussion on the radio recently between Newfoundland and Labrador’s Minister of Education and aprofessor from Memorial University’s Math Department. They were debating the efficacy of the math curriculum in the province’s school system. As a parent of a grade 3 student, I have my own thoughts on how the curriculum is affecting kids’ math skills (and their anxiety levels, but let’s not go there. The professor echoed the concern that parents, teachers and students have been expressing: quite simply, it’s not working. Far too many children are failing math and are struggling with the both the content and pace of the required modules. Why am I telling you this? One particular comment made by the Minister of Education struck me. She said that there was evidence to suggest that this curriculum should work. While I’m always delighted to see the evidence based practice model being used, particularly for the betterment of my kids’education, it is dismaying to see that it is not always applied well. In this particular case, evidence was collected from somewhere and a decision was made to implement a new math curriculum based on the gathered evidence. Assuming that this truly was good evidence upon which to base such a decision, then I would have to concede that the appropriate steps were taken up until that point. Unfortunately, it appears that the entire process stopped there. As we know, one of the most important components of a thorough ebp‐based implementation is an internal evaluation. What might work somewhere else is not guaranteed to work in another environment, and it is essential to determine why an implementation or intervention worked or didn’t work. It would seem, in this case, that formal evaluations of the effectiveness of the new math curriculum have not been performed and therefore, the powers that be rely solely on the fact that it worked somewhere else. This is not evidence based

  1. Radioimmunoassay for measurement of thyroxine (T4) and triiodothyonine (T3) in blood serum

    International Nuclear Information System (INIS)

    Chopra, I.J.

    1975-01-01

    This invention relates to a highly accurate, rapid and simple estimation of thyroxine (T 4 ) directly from blood serum and also relates to the accurate measurement of triiodo-L-thyronine (T 3 ) directly from blood serum. More specifically, the invention relates to a rapid, specific and reliable radioimmunoassay (RIA) technique for measurement of both T 4 and T 3 in unextracted serum. The method requires very small amounts of serum, e.g., 25 microliters (μl) to measure T 4 concentration in nearly all specimens representing clinical states of eu-, hypo- and hyperthyroidism, and 250 μl to measure T 3 concentrations in specimens representing most clinical states

  2. CD4+ T Cells Mediate Aspergillosis Vaccine Protection.

    Science.gov (United States)

    Diaz-Arevalo, Diana; Kalkum, Markus

    2017-01-01

    Adaptive effector CD4 + T cells play essential roles in the defense against fungal infections, especially against invasive aspergillosis (IA). Such protective CD4 + T cells can be generated through immunization with specialized antifungal vaccines, as has been demonstrated for pulmonary Aspergillus fumigatus infections in mouse experiments. Adaptive transfer of fungal antigen-specific CD4 + T cells conferred protection onto non-immunized naive mice, an experimental approach that could potentially become a future treatment option for immunosuppressed IA patients, focusing on the ultimate goal to improve their otherwise dim chances for survival. Here, we describe the different techniques to analyze CD4 + T cell immune responses after immunization with a recombinant fungal protein. We present three major methods that are used to analyze the role of CD4 + T cells in protection against A. fumigatus challenge. They include (1) transplantation of CD4 + T cells from vaccinated mice into immunosuppressed naive mice, observing increasing protection of the cell recipients, (2) depletion of CD4 + T cells from vaccinated mice, which abolishes vaccine protection, and (3) T cell proliferation studies following stimulation with overlapping synthetic peptides or an intact protein vaccine. The latter can be used to validate immunization status and to identify protective T cell epitopes in vaccine antigens. In the methods detailed here, we used versions of the well-studied Asp f3 protein expressed in a bacterial host, either as the intact full length protein or its N-terminally truncated version, comprised of residues 15-168. However, these methods are generally applicable and can well be adapted to study other protein-based subunit vaccines.

  3. Acanthamoeba belonging to T3, T4, and T11: genotypes isolated from air-conditioning units in Santiago, Chile.

    Science.gov (United States)

    Astorga, Berbeli; Lorenzo-Morales, Jacob; Martín-Navarro, Carmen M; Alarcón, Verónica; Moreno, Johanna; González, Ana C; Navarrete, Elizabeth; Piñero, José E; Valladares, Basilio

    2011-01-01

    Free-living amoebae (FLA) of the genus Acanthamoeba are widely distributed in the environment, in the air, soil, and water, and have also been isolated from air-conditioning units. The objective of this work was to investigate the presence of this genus of FLA in the air-conditioning equipment at the Institute of Public Health of Chile in Santiago, Chile. Water and air samples were collected from air-conditioning systems and were checked for the presence of Acanthamoeba spp. Positive samples were further classified at the genotype level after sequencing the highly variable diagnostic fragment 3 (DF3) region of the 18S rRNA gene. This is the first report of the T3, T4, and T11 genotypes of Acanthamoeba in air-conditioning units from Chile. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals in Chile as this pathogen is emerging as a risk for human health worldwide. © 2011 The Author(s) Journal of Eukaryotic Microbiology © 2011 International Society of Protistologists.

  4. Radioimmunoassay of serum T3, T4 and TSH during anesthesia and operation

    International Nuclear Information System (INIS)

    Gosheva-Antonova, Ts.; Zakharieva, B.; Kurtev, I.

    1987-01-01

    The serum concentrations of thyroxine (T 3 ), triiodothyronine (T 4 ) and thyroid-stimulating hormone (TSH) were determined in 31 partients before and during urologic operations on the 30th and 60th minute since the onset of the operation, performed under endotracheal halotane or neuroleptanesthesia (NLA) in assisted breathing and intravenous drip anesthesia with ketalar-diazepam in spontaneous breathing. There was statistically significant rise in T 4 level, decrease in T 3 and negligible changes in TSH level, in patients operated under halotane anesthesia. In those operated under NLA, T 4 tended initially to be elevated, with subseguent fall to starting level, with a tendency toward rise in TSH and stable unchanged T 3 level. Ketalar-diazepam anesthesia was applied only to patients subjected to transurethral resections. T 4 in them tended to be decreased, while T 3 and TSH showed negligible changes. Since the operations of patients anesthesized with halotane and NLA had similar localizations and severity, the differences in the thyroid hormone reactions could be associated with the type of anesthesia. The negligible changes in TSH are highly suggestive that this hormone is not influenced by the operation stress and anesthetics, and does hot exert regulating effect upon the thyroid status under these conditions. The milder reactions in patients operated under ketalar-diazepam anestesia may largely be associated with the milder operation stress in transurethal resection

  5. Thyroid hormones in the elderly sick: "T4 euthyroidism".

    Science.gov (United States)

    Burrows, A W; Shakespear, R A; Hesch, R D; Cooper, E; Aickin, C M; Burke, C W

    1975-11-22

    Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital.

  6. Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response.

    Science.gov (United States)

    Newton, Jared M; Flores-Arredondo, Jose H; Suki, Sarah; Ware, Matthew J; Krzykawska-Serda, Martyna; Agha, Mahdi; Law, Justin J; Sikora, Andrew G; Curley, Steven A; Corr, Stuart J

    2018-02-22

    Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response. More specifically we show that multi- and singlet-dose RFT promote an increase in tumor volume in immune competent Balb/c mice, which does not occur in athymic nude models. Further leukocyte subset analysis at 24, 48, and 120 hours after a single RFT show a rapid increase in tumoral trafficking of CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis reveals an increase in numerous pro-inflammatory cytokines and chemokines associated with enhanced T-cell trafficking. Overall, these data demonstrate that non-invasive RFT could be an effective immunomodulatory strategy in solid tumors, especially for enhancing the tumoral trafficking of lymphocytes, which is currently a major hindrance of numerous cancer immunotherapeutic strategies.

  7. CD4+ T-cell epitope prediction using antigen processing constraints.

    Science.gov (United States)

    Mettu, Ramgopal R; Charles, Tysheena; Landry, Samuel J

    2016-05-01

    T-cell CD4+ epitopes are important targets of immunity against infectious diseases and cancer. State-of-the-art methods for MHC class II epitope prediction rely on supervised learning methods in which an implicit or explicit model of sequence specificity is constructed using a training set of peptides with experimentally tested MHC class II binding affinity. In this paper we present a novel method for CD4+ T-cell eptitope prediction based on modeling antigen-processing constraints. Previous work indicates that dominant CD4+ T-cell epitopes tend to occur adjacent to sites of initial proteolytic cleavage. Given an antigen with known three-dimensional structure, our algorithm first aggregates four types of conformational stability data in order to construct a profile of stability that allows us to identify regions of the protein that are most accessible to proteolysis. Using this profile, we then construct a profile of epitope likelihood based on the pattern of transitions from unstable to stable regions. We validate our method using 35 datasets of experimentally measured CD4+ T cell responses of mice bearing I-Ab or HLA-DR4 alleles as well as of human subjects. Overall, our results show that antigen processing constraints provide a significant source of predictive power. For epitope prediction in single-allele systems, our approach can be combined with sequence-based methods, or used in instances where little or no training data is available. In multiple-allele systems, sequence-based methods can only be used if the allele distribution of a population is known. In contrast, our approach does not make use of MHC binding prediction, and is thus agnostic to MHC class II genotypes. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Report of the Snowmass M6 Working Group on high intensity proton sources

    Energy Technology Data Exchange (ETDEWEB)

    Weiren Chou and J. Wei

    2002-08-20

    The U.S. high-energy physics program needs an intense proton source, a 1-4 MW Proton Driver (PD), by the end of this decade. This machine will serve as a stand-alone facility that will provide neutrino superbeams and other high intensity secondary beams such as kaons, muons, neutrons, and anti-protons (cf. E1 and E5 group reports) and also serve as the first stage of a neutrino factory (cf. M1 group report). It can also be a high brightness source for a VLHC. Based on present accelerator technology and project construction experience, it is both feasible and cost-effective to construct a 1-4 MW Proton Driver. Two recent PD design studies have been made, one at FNAL and the other at the BNL. Both designed PD's for 1 MW proton beams at a cost of about U.S. $200M (excluding contingency and overhead) and both designs were upgradeable to 4 MW. An international collaboration between FNAL, BNL and KEK on high intensity proton facilities is addressing a number of key design issues. The superconducting (sc) RF cavities, cryogenics, and RF controls developed for the SNS can be directly adopted to save R&D efforts, cost, and schedule. PD studies are also actively being pursued at Europe and Japan.

  9. Re-initiation repair in bacteriophage T4

    International Nuclear Information System (INIS)

    Cupido, M.

    1981-01-01

    Irradiation of bacteriophage T4 with ultraviolet light induces the formation of pyrimidine dimers in its DNA. These dimers hamper replication of DNA and, to a lesser extent, transcription of DNA after its infection of bacteria. A number of pathways enable phage T4 to multiply dimer-containing DNA. One of these pathways has been named replication repair and is described in this thesis. The properties of two phage strains, unable to perform replication repair, have been studied to obtain a picture of the repair process. The mutations in these strains that affect replication repair have been located on the genomic map of T4. (Auth.)

  10. CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

    Science.gov (United States)

    Zhang, Xiaolong; Chang Li, Xian; Xiao, Xiang; Sun, Rui; Tian, Zhigang; Wei, Haiming

    2013-01-01

    The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg. PMID:24155942

  11. Clonal expansion of CD4+ Cytotoxic T Lymphocytes in IgG4-related disease

    Science.gov (United States)

    Mattoo, Hamid; Mahajan, Vinay S.; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S.; Kulikova, Maria; Drijvers, Jefte M.; Daccache, Joe; Carruthers, Mollie N.; Castellino, Flavia; Stone, James R.; Stone, John H.; Pillai, Shiv

    2016-01-01

    Background IgG4-related disease (IgG4-RD) is a systemic condition of unknown etiology, characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4+ T cells constitute the major inflammatory cell population in IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T cell subsets in IgG4-RD subjects based on their clonal expansion and their ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4+ effector/memory T cells (TEM) in a cohort of 101 IgG4-related disease (IgG4-RD) patients. These expanded cells were characterized by gene expression analysis and flow cytometry. Next-generation sequencing of the T cell receptor β chain gene was performed on CD4+SLAMF7+ CTLs and CD4+GATA3+ TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined using quantitative multi-color imaging. Results CD4+ effector/memory T cells with a cytolytic phenotype were expanded in IgG4-RD patients. Next-generation sequencing revealed prominent clonal expansions of these CD4+CTLs but not CD4+GATA3+ memory TH2 cells in subjects with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally-expanded CD4+CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B cell depletion was associated with a reduction in disease-associated CD4+ CTLs Conclusions IgG4-RD is prominently linked to clonally-expanded, IL-1β, and TGF- β1 secreting, CD4+ CTLs in peripheral blood as well as in inflammatory tissue lesions. These active, terminally-differentiated, cytokine-secreting effector CD4+ T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. PMID:26971690

  12. Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

    Science.gov (United States)

    Kirstein, Frank; Nieuwenhuizen, Natalie E; Jayakumar, Jaisubash; Horsnell, William G C; Brombacher, Frank

    2016-06-01

    TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. HIV-1 intersection with CD4 T cell vesicle exocytosis: intercellular communication goes viral

    Directory of Open Access Journals (Sweden)

    Helena eSoares

    2014-09-01

    Full Text Available In cells of the immune system the secretion of extracellular vesicles is modulated through cellular activation. In particular, T cell activation is achieved through cell-cell contacts with antigen presenting cells and the consequent formation of a specialized signaling junction called the immunological synapse. Recent works on CD4 T cells have elucidated that cognate antigen recognition by the T cell receptor (TCR engages two distinct exocytic events. The first, involves the exocytic targeting of signaling molecules at the synaptic membrane and drives the functional architecture of the immunological synapse. The second, enlists the extracellular secretion of the TCR itself, once the functional architecture of the immunological synapse is accomplished. HIV-1, a human lymphotropic virus, has evolved sophisticated mechanisms to co-opt CD4 T cell physiology. Notably, it has become apparent that HIV-1 intersects the regulated secretory system of CD4 T cells in order to bud from the plasma membrane of the infected cell and to promote bystander cell death. Here, I review the relevance of CD4 vesicle exocytosis to immune regulation and to HIV-1 pathogenesis and discuss their potential therapeutic applications.

  14. CD4/CD8/Dendritic cell complexes in the spleen: CD8+ T cells can directly bind CD4+ T cells and modulate their response

    Science.gov (United States)

    Barinov, Aleksandr; Galgano, Alessia; Krenn, Gerald; Tanchot, Corinne; Vasseur, Florence

    2017-01-01

    CD4+ T cell help to CD8+ T cell responses requires that CD4+ and CD8+ T cells interact with the same antigen presenting dendritic cell (Ag+DC), but it remains controversial whether helper signals are delivered indirectly through a licensed DC and/or involve direct CD4+/CD8+ T cell contacts and/or the formation of ternary complexes. We here describe the first in vivo imaging of the intact spleen, aiming to evaluate the first interactions between antigen-specific CD4+, CD8+ T cells and Ag+DCs. We show that in contrast to CD4+ T cells which form transient contacts with Ag+DC, CD8+ T cells form immediate stable contacts and activate the Ag+DC, acquire fragments of the DC membranes by trogocytosis, leading to their acquisition of some of the DC properties. They express MHC class II, and become able to present the specific Marilyn peptide to naïve Marilyn CD4+ T cells, inducing their extensive division. In vivo, these CD8+ T cells form direct stable contacts with motile naïve CD4+ T cells, recruiting them to Ag+DC binding and to the formation of ternary complexes, where CD4+ and CD8+ T cells interact with the DC and with one another. The presence of CD8+ T cells during in vivo immune responses leads to the early activation and up-regulation of multiple functions by CD4+ T lymphocytes. Thus, while CD4+ T cell help is important to CD8+ T cell responses, CD8+ T cells can interact directly with naïve CD4+ T cells impacting their recruitment and differentiation. PMID:28686740

  15. Summary of the Very Large Hadron Collider Physics and Detector subgroup

    International Nuclear Information System (INIS)

    Denisov, D.; Keller, S.

    1996-01-01

    We summarize the activity of the Very Large Hadron Collider Physics and Detector subgroup during Snowmass 96. Members of the group: M. Albrow, R. Diebold, S. Feher, L. Jones, R. Harris, D. Hedin, W. Kilgore, J. Lykken, F. Olness, T. Rizzo, V. Sirotenko, and J. Womersley. 9 refs

  16. A novel differentiation pathway from CD4T cells to CD4T cells for maintaining immune system homeostasis.

    Science.gov (United States)

    Zhao, X; Sun, G; Sun, X; Tian, D; Liu, K; Liu, T; Cong, M; Xu, H; Li, X; Shi, W; Tian, Y; Yao, J; Guo, H; Zhang, D

    2016-04-14

    CD4(+) T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4(+) T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4(-)CD8(-)NK1.1(-) double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4(+) rather than CD8(+) T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4(+) T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases.

  17. T/sub 4/ radioimmunoassay with ion-exchange resin separation

    Energy Technology Data Exchange (ETDEWEB)

    Michael, J D; Modha, K [Hoechst Pharmaceuticals Research Ltd., Milton Keynes (UK)

    1977-05-28

    An explanation is provided for the reports of falsely low values of serum-thyroxine (T/sub 4/) measured by radioimmunoassay (RIA), particularly in sera containing raised concentrations of thyroxine-binding globulin (TBG) (Burr, W.A., Evans, S.E., Hogan, T.C., 1977, Lancet, April 2, 757). A re-examination of the assay technique used in commercial RIA kits ('RIA-gnost T/sub 3/' and 'RIA-gnost T/sub 4/', Behring Diagnostics) showed that blocking of binding proteins by 8-anilino-1-naphthalene sulphonic acid (ANS) was incomplete in sera with raised TBG levels. Spectroscopic determination of the blocker concentration during the time the solution was in contact with the ion exchange resin showed that 98% of the ANS was removed from solution by 10 min contact with the resin, yet 60 min was required to absorb the free T/sub 4/. There was therefore ample time for unblocked TBG to recombine with free T/sub 4/ which was then misclassified as antibody-bound T/sub 4/. The assay technique used in the kits was therefore modified. The less polar TBG blocking agent, ethylmercurithiosalicylate (merthiolate), replaced ANS and it was demonstrated that accurate T/sub 3/ and T/sub 4/ measurements in high TBG sera could be made by resin-separation RIA without resorting to prior denaturation or alcohol extraction.

  18. Phage T4 SegB protein is a homing endonuclease required for the preferred inheritance of T4 tRNA gene region occurring in co-infection with a related phage.

    Science.gov (United States)

    Brok-Volchanskaya, Vera S; Kadyrov, Farid A; Sivogrivov, Dmitry E; Kolosov, Peter M; Sokolov, Andrey S; Shlyapnikov, Michael G; Kryukov, Valentine M; Granovsky, Igor E

    2008-04-01

    Homing endonucleases initiate nonreciprocal transfer of DNA segments containing their own genes and the flanking sequences by cleaving the recipient DNA. Bacteriophage T4 segB gene, which is located in a cluster of tRNA genes, encodes a protein of unknown function, homologous to homing endonucleases of the GIY-YIG family. We demonstrate that SegB protein is a site-specific endonuclease, which produces mostly 3' 2-nt protruding ends at its DNA cleavage site. Analysis of SegB cleavage sites suggests that SegB recognizes a 27-bp sequence. It contains 11-bp conserved sequence, which corresponds to a conserved motif of tRNA TpsiC stem-loop, whereas the remainder of the recognition site is rather degenerate. T4-related phages T2L, RB1 and RB3 contain tRNA gene regions that are homologous to that of phage T4 but lack segB gene and several tRNA genes. In co-infections of phages T4 and T2L, segB gene is inherited with nearly 100% of efficiency. The preferred inheritance depends absolutely on the segB gene integrity and is accompanied by the loss of the T2L tRNA gene region markers. We suggest that SegB is a homing endonuclease that functions to ensure spreading of its own gene and the surrounding tRNA genes among T4-related phages.

  19. 26 CFR 1.846-4T - Effective dates (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Effective dates (temporary). 1.846-4T Section 1.846-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Other Insurance Companies § 1.846-4T Effective dates (temporary). (a) [Reserved...

  20. Night work, long working hours, psychosocial work stress and cortisol secretion in mid-life: evidence from a British birth cohort.

    Science.gov (United States)

    Thomas, C; Hertzman, C; Power, C

    2009-12-01

    To examine the relationships between exposure to workplace factors (night work, extended working hours, psychosocial work stress) and cortisol secretion, and to test whether workplace factors interact, resulting in combined effects. Multiple linear and logistic regression was used to test relationships between workplace factors and cortisol secretion in the 1958 British birth cohort at 45 years. Salivary cortisol was measured twice on the same day to capture the post-waking decline, facilitating the analysis of different cortisol patterns: (1) time 1 (T1, 45 minutes post-waking); (2) time 2 (T2, 3 h after T1); (3) average 3 h exposure from T1 to T2 cortisol; and (4) T1 to T2 change. To identify altered diurnal cortisol patterns we calculated: (1) flat T1-T2 change in cortisol; (2) top 5% T1; (3) bottom 5% T1; and (4) T1 hypo-secretion or hyper-secretion. Models were adjusted for socioeconomic position at birth and in adulthood, qualifications, marital status, dependent children, and smoking status. 25% of men and 8% of women were exposed to >1 workplace factor (night work, extended work hours, job strain). Night work was associated with a 4.28% (95% CI 1.21 to 7.45) increase in average 3 h cortisol secretion independently of job strain or work hours. Night workers not exposed to job strain had elevated T1 cortisol (5.81%, 95% CI 1.61 to 10.19), although for T2 cortisol it was night workers exposed to low job control who had elevated levels (11.72%, 95% CI 4.40 to 19.55). Men (but not women) working >48 h/week had lower average 3 h cortisol secretion (4.55%, 95% CI -8.43 to -0.50). There were no main effects for psychosocial work stress. All associations for T2 and average 3 h cortisol secretion weakened slightly after adjustment for confounding factors, but associations for T1 cortisol were unaffected by adjustment. Our study suggests that night work in particular is associated with elevated cortisol secretion and that cortisol dysregulation may exist in subgroups

  1. An improved 96-well turbidity assay for T4 lysozyme activity.

    Science.gov (United States)

    Toro, Tasha B; Nguyen, Thao P; Watt, Terry J

    2015-01-01

    T4 lysozyme (T4L) is an important model system for investigating the relationship between protein structure and function. Despite being extensively studied, a reliable, quantitative activity assay for T4L has not been developed. Here, we present an improved T4L turbidity assay as well as an affinity-based T4L expression and purification protocol. This assay is designed for 96-well format and utilizes conditions amenable for both T4L and other lysozymes. This protocol enables easy, efficient, and quantitative characterization of T4L variants and allows comparison between different lysozymes. Our method: •Is applicable for all lysozymes, with enhanced sensitivity for T4 lysozyme compared to other 96-well plate turbidity assays;•Utilizes standardized conditions for comparing T4 lysozyme variants and other lysozymes; and•Incorporates a simplified expression and purification protocol for T4 lysozyme.

  2. T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes

    DEFF Research Database (Denmark)

    Wilson, A; Ewing, T; Owens, T

    1988-01-01

    . No positive cells were detected among Ly-2-L3T4- thymocytes from V beta 8-negative SJL mice. In contrast to the adult thymus, Ly-2-L3T4- cells from embryonic CBA thymus lacked F23.1-positive cells. Subsets of adult CBA Ly-2-L3T4- thymocytes were separated to determine which expressed V beta 8. The major...... B2A2-M1/69- and Pgp-1+ all included strongly F23.1-positive cells. A minor subset, negative for most markers except Pgp-1 and presumed on the basis of this phenotype and some reconstitution studies to include the earliest intrathymic precursors, contained 28% F23.1-positive cells. However, no F.23...

  3. Frontoparietal tDCS Benefits Visual Working Memory in Older Adults With Low Working Memory Capacity.

    Science.gov (United States)

    Arciniega, Hector; Gözenman, Filiz; Jones, Kevin T; Stephens, Jaclyn A; Berryhill, Marian E

    2018-01-01

    Working memory (WM) permits maintenance of information over brief delays and is an essential executive function. Unfortunately, WM is subject to age-related decline. Some evidence supports the use of transcranial direct current stimulation (tDCS) to improve visual WM. A gap in knowledge is an understanding of the mechanism characterizing these tDCS linked effects. To address this gap, we compared the effects of two tDCS montages designed on visual working memory (VWM) performance. The bifrontal montage was designed to stimulate the heightened bilateral frontal activity observed in aging adults. The unilateral frontoparietal montage was designed to stimulate activation patterns observed in young adults. Participants completed three sessions (bilateral frontal, right frontoparietal, sham) of anodal tDCS (20 min, 2 mA). During stimulation, participants performed a visual long-term memory (LTM) control task and a visual WM task. There was no effect of tDCS on the LTM task. Participants receiving right unilateral tDCS showed a WM benefit. This pattern was most robust in older adults with low WM capacity. To address the concern that the key difference between the two tDCS montages could be tDCS over the posterior parietal cortex (PPC), we included new analyses from a previous study applying tDCS targeting the PPC paired with a recognition VWM task. No significant main effects were found. A subsequent experiment in young adults found no significant effect of either tDCS montage on either task. These data indicate that tDCS montage, age and WM capacity should be considered when designing tDCS protocols. We interpret these findings as suggestive that protocols designed to restore more youthful patterns of brain activity are superior to those that compensate for age-related changes.

  4. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien who...

  5. Intervalos de referencia para concentraciones séricas de T3 y T4. Estudio preliminar

    Directory of Open Access Journals (Sweden)

    Cecilia Miranda Pantoja

    2013-12-01

    Full Text Available Fundamento: la determinación cuantitativa de las hormonas tiroideas T3 y T4 reviste gran importancia en el diagnóstico y la evaluación del hipertiroidismo, en especial del hipertiroidismo aislado causado por T3.Objetivo: establecer los intervalos de referencia de T3 y T4 en el laboratorio de medicina nuclear del Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos. Métodos: estudio descriptivo y prospectivo realizado mediante el método de radioinmunoanálisis, competencia que se establece entre la T3 y T4 sin marcar, y la marcada por un número limitado de los sitios de unión del anticuerpo específico. Al hacer reaccionar una cantidad fija de trazador y anticuerpo con diferentes cantidades del ligando sin marcar, la cantidad de trazador unido por el anticuerpo será inversamente proporcional a la concentración del ligando sin marcar. Resultados: los valores obtenidos se describen según una distribución gaussiana (media aritmética = 117, desviación estándar =31 para T4; media aritmética = 2,64, desviación estándar = 0,64 para T3, comprobado mediante un test de Chi cuadrado. Los rangos de valores normales obtenidos fueron de de 55 – 178 nmol/L y 1,4 – 3,9 nmol/L para T4 y T3 respectivamente. Conclusiones: los intervalos de referencia obtenidos resultaron más amplios que los propuestos por el productor, sobre todo en el caso de T4.

  6. PROTEOLYTIC REMOVAL OF THE CARBOXYL TERMINUS OF THE T4 GENE 32 HELIX-DESTABILIZING PROTEIN ALTERS THE T4 IN VITRO REPLICATION COMPLEX

    Energy Technology Data Exchange (ETDEWEB)

    Burke, R.L.; Alberts, B.M.; Hosoda, J.

    1980-07-01

    The proteolytic removal of about 60 amino acids from the COOH terminus of the bacteriophage T4 helix-destabilizing protein (gene 32 protein) produces 32*I, a 27,000-dalton fragment which still binds tightly and cooperatively to single-stranded DNA. The substitution of 32*I protein for intact 32 protein in the seven-protein T4 replication complex results in dramatic changes in some of the reactions catalyzed by this in vitro DNA replication system, while leaving others largely unperturbed. (1) Like intact 32 protein, the 32*I protein promotes DNA synthesis by the DNA polymerase when the T4 polymerase accessory proteins (gene 44/62 and 45 proteins) are also present. The host helix-destabilizing protein (Escherichia coli ssb protein) cannot replace the 32*I protein for this synthesis. (2) Unlike intact 32 protein, 32*I protein strongly inhibits DNA synthesis catalyzed by the T4 DNA polymerase alone on a primed single-stranded DNA template. (3) Unlike intact 32 protein, the 32*I protein strongly inhibits RNA primer synthesis catalyzed by the T4 gene 41 and 61 proteins and also reduces the efficiency of RNA primer utilization. As a result, de novo DNA chain starts are blocked completely in the complete T4 replication system, and no lagging strand DNA synthesis occurs. (4) The 32*I protein does not bind to either the T4 DNA polymerase or to the T4 gene 61 protein in the absence of DNA; these associations (detected with intact 32 protein) would therefore appear to be essential for the normal control of 32 protein activity, and to account at least in part for observations 2 and 3, above. We propose that the COOH-terminal domain of intact 32 protein functions to guide its interactions with the T4 DNA polymerase and the T4 gene 61 RNA-priming protein. When this domain is removed, as in 32*I protein, the helix destabilization induced by the protein is controlled inadequately, so that polymerizing enzymes tend to be displaced from the growing 3{prime}-OH end of a

  7. Interleukin 4-producing CD4+ T cells in the skin of cats with allergic dermatitis.

    Science.gov (United States)

    Roosje, P J; Dean, G A; Willemse, T; Rutten, V P M G; Thepen, T

    2002-03-01

    Lesional skin of cats with allergic dermatitis has a cellular infiltrate and a CD4/CD8 ratio comparable to that in humans with atopic dermatitis. CD4+ helper T cells and in particular cells belonging to the Th2 subset play an important role in disease pathogenesis in humans. We investigated the cytokine pattern of CD4+ T cells in situ, with special emphasis on the putative presence of cells producing interleukin 4 (IL4), in cats with allergic dermatitis. Immunohistochemical procedures were used to determine that CD4+ T cells in lesional and nonlesional skin of cats with allergic dermatitis can produce IL4, as occurs in humans. Lesional and nonlesional skin of cats with allergic dermatitis had significantly more IL4+ T cells (P = 0.001) than did skin of healthy control cats. Double staining indicated that all IL4+ cells were positive for pan-T or CD4 markers. Double labeling for mast cell chymase and IL4 stained primarily different cells. Western blotting demonstrated cross-reactivity between the antibody against human IL4 and a feline recombinant IL4. These results indicate that IL4 is primarily produced by CD4+ T cells and is also present in clinically uninvolved skin, indicating a role in the pathogenesis of allergic dermatitis in cats.

  8. Cytokines affecting CD4+T regulatory cells in transplant tolerance. III. Interleukin-5 (IL-5) promotes survival of alloantigen-specific CD4+ T regulatory cells.

    Science.gov (United States)

    Hall, Bruce M; Plain, Karren M; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine M; Nomura, Masaru; Boyd, Rochelle; Hodgkinson, Suzanne J

    2017-08-01

    CD4 + T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4 + CD25 + FOXP3 + Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg. This study examined if recombinant IL-5(rIL-5) promoted survival of tolerant CD4 + , especially CD4 + CD25 + T cells. CD4 + T cells, from DA rats tolerant to fully allogeneic PVG heart allografts surviving over 100days without on-going immunosuppression, were cultured with PVG alloantigen and rIL-5. The ability of these cells to adoptively transfer tolerance to specific-donor allograft and suppress normal CD4 + T cell mediated rejection in adoptive DA hosts was examined. Tolerant CD4 + CD25 + T cells' response to rIL-5 and expression of IL-5Rα was also assessed. rIL-5 was sufficient to promote transplant tolerance mediating CD4 + T cells' survival in culture with specific-donor alloantigen. Tolerant CD4 + T cells cultured with rIL-5 retained the capacity to transfer alloantigen-specific tolerance and inhibited naïve CD4 + T cells' capacity to effect specific-donor graft rejection. rIL-5 promoted tolerant CD4 + CD25 + T cells' proliferation in vitro when stimulated with specific-donor but not third-party stimulator cells. Tolerant CD4 + CD25 + T cells expressed IL-5Rα. This study demonstrated that IL-5 promoted the survival of alloantigen-specific CD4 + CD25 + T cells that mediate transplant tolerance. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. IL-15 augments TCR-induced CD4+ T cell expansion in vitro by inhibiting the suppressive function of CD25 High CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Tom L Van Belle

    Full Text Available Due to its critical role in NK cell differentiation and CD8(+ T cell homeostasis, the importance of IL-15 is more firmly established for cytolytic effectors of the immune system than for CD4(+ T cells. The increased levels of IL-15 found in several CD4(+ T cell-driven (auto- immune diseases prompted us to examine how IL-15 influences murine CD4(+ T cell responses to low dose TCR-stimulation in vitro. We show that IL-15 exerts growth factor activity on both CD4(+ and CD8(+ T cells in a TCR-dependent and Cyclosporin A-sensitive manner. In CD4(+ T cells, IL-15 augmented initial IL-2-dependent expansion and once IL-15Rα was upregulated, IL-15 sustained the TCR-induced expression of IL-2/15Rβ, supporting proliferation independently of secreted IL-2. Moreover, IL-15 counteracts CD4(+ T cell suppression by a gradually expanding CD25(HighCD4(+ T cell subset that expresses Foxp3 and originates from CD4(+CD25(+ Tregs. These in vitro data suggest that IL-15 may dramatically strengthen the T cell response to suboptimal TCR-triggering by overcoming an activation threshold set by Treg that might create a risk for autoimmune pathology.

  10. Structure and expression of the human and mouse T4 genes

    International Nuclear Information System (INIS)

    Maddon, P.J.; Molineaux, S.M.; Maddon, D.F.; Zimmerman, K.A.; Godfrey, M.; Alt, F.W.; Chess, L.; Axel, R.

    1987-01-01

    The T4 molecule may serve as a T-cell receptor recognizing molecules on the surface of specific target cells and also serves as the receptor for the human immunodeficiency virus. To define the mechanisms of interaction of T4 with the surface of antigen-presenting cells as well as with human immunodeficiency virus, the authors have further analyzed the sequence, structure, and expression of the human and mouse T4 genes. T4 consists of an extracellular segment comprised of a leader sequence followed by four tandem variable-joining (VJ)-like domains, a transmembrane domain, and A cytoplasmic segment. The structural domains of the T4 protein deduced from amino acid sequence are precisely reflected in the intron-exon organization of the gene. Analysis of the expression of the T4 gene indicates that T4 RNA is expressed not only in T lymphocytes, but in B cells, macrophages, and granulocytes. T4 is also expressed in a developmentally regulated manner in specific regions of the brain. It is, therefore, possible that T4 plays a more general role in mediating cell recognition events that are not restricted to the cellular immune response

  11. Task-shifting of CD4 T cell count monitoring by the touchscreen-based Muse™ Auto CD4/CD4% single-platform system for CD4 T cell numeration: Implication for decentralization in resource-constrained settings.

    Science.gov (United States)

    Kouabosso, André; Mossoro-Kpinde, Christian Diamant; Bouassa, Ralph-Sydney Mboumba; Longo, Jean De Dieu; Mbeko Simaleko, Marcel; Grésenguet, Gérard; Bélec, Laurent

    2018-04-01

    The accuracy of CD4 T cell monitoring by the recently developed flow cytometry-based CD4 T cell counting Muse™ Auto CD4/CD4% Assay analyzer (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) was evaluated in trained lay providers against laboratory technicians. After 2 days of training on the Muse™ Auto CD4/CD4% analyzer, EDTA-blood samples from 6 HIV-positive and 4 HIV-negative individuals were used for CD4 T cell counting in triplicate in parallel by 12 trained lay providers as compared to 10 lab technicians. Mean number of CD4 T cells in absolute number was 829 ± 380 cells/μl by lay providers and 794 ± 409 cells/μl by technicians (P > 0.05); and in percentage 36.2 ± 14.8%CD4 by lay providers and 36.1 ± 15.0%CD4 by laboratory technician (P > 0.05). The unweighted linear regression and Passing-Bablok regression analyses on CD4 T cell results expressed in absolute count revealed moderate correlation between CD4 T cell counts obtained by lay providers and lab technicians. The mean absolute bias measured by Bland-Altman analysis between CD4 T cell/μl obtained by lay providers and lab technicians was -3.41 cells/μl. Intra-assay coefficient of variance (CV) of Muse™ Auto CD4/CD4% in absolute number was 10.1% by lay providers and 8.5% by lab technicians (P > 0.05), and in percentage 5.5% by lay providers and 4.4% by lab technicians (P > 0.05). The inter-assay CV of Muse™ Auto CD4/CD4% in absolute number was 13.4% by lay providers and 10.3% by lab technicians (P > 0.05), and in percentage 7.8% by lay providers and 6.9% by lab technicians (P > 0.05). The study demonstrates the feasibility of CD4 T cell counting using the alternative flow cytometer Muse™ Auto CD4/CD4% analyzer by trained lay providers and therefore the practical possibility of decentralization CD4 T cell counting to health community centers. Copyright © 2018. Published by Elsevier B.V.

  12. CD4+CD25hiFOXP3+ cells in cord blood of neonates born from filaria infected mother are negatively associated with CD4+Tbet+ and CD4+RORγt+ T cells.

    Science.gov (United States)

    Ateba-Ngoa, Ulysse; Mombo-Ngoma, Ghyslain; Zettlmeissl, Eva; van der Vlugt, Luciën E P M; de Jong, Sanne E; de Jong, Sanne; Matsiegui, Pierre-Blaise; Ramharter, Michael; Kremsner, Peter G; Yazdanbakhsh, Maria; Adegnika, Ayola Akim

    2014-01-01

    Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses. Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3. No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively). Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

  13. Performance Evaluations for IEEE 802.15.4-based IoT Smart Home Solution

    Directory of Open Access Journals (Sweden)

    Nga Dinh

    2016-09-01

    Full Text Available The Internet of Things (IoT is going to be a market-changing force for a variety of real-time applications such as e-healthcare, home automation, environmental monitoring, and industrial automation. Low power wireless communication protocols offering long lifetime and high reliability such as the IEEE 802.15.4 standard have been a key enabling technology for IoT deployments and are deployed for home automation recently. The issues of the IEEE 802.15.4 networks have moved from theory to real world deployments. The work presented herein intends to demonstrate the use of the IEEE 802.15.4 standard in recent IoT commercial products for smart home applications: the Smart Home Starter Kit. The contributions of the paper are twofold. First, the paper presents how the IEEE 802.15.4 standard is employed in Smart Home Starter Kit. In particular, network topology, network operations, and data transfer mode are investigated. Second, network performance metrics such as end-to-end (E2E delay and frame reception ratio (FRR are evaluated by experiments. In addition, the paper discusses several directions for future improvements of home automation commercial products.

  14. PKM2-dependent metabolic reprogramming in CD4+ T cells is crucial for hyperhomocysteinemia-accelerated atherosclerosis.

    Science.gov (United States)

    Lü, Silin; Deng, Jiacheng; Liu, Huiying; Liu, Bo; Yang, Juan; Miao, Yutong; Li, Jing; Wang, Nan; Jiang, Changtao; Xu, Qingbo; Wang, Xian; Feng, Juan

    2018-06-01

    Inflammation mediated by activated T cells plays an important role in the initiation and progression of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis in ApoE -/- mice. Homocysteine (Hcy) activates T cells to secrete proinflammatory cytokines, especially interferon (IFN)-γ; however, the precise mechanisms remain unclear. Metabolic reprogramming is critical for T cell inflammatory activation and effector functions. Our previous study demonstrated that Hcy regulates T cell mitochondrial reprogramming by enhancing endoplasmic reticulum (ER)-mitochondria coupling. In this study, we further explored the important role of glycolysis-mediated metabolic reprogramming in Hcy-activated CD4 + T cells. Mechanistically, Hcy-activated CD4 + T cell increased the protein expression and activity of pyruvate kinase muscle isozyme 2 (PKM2), the final rate-limiting enzyme in glycolysis, via the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin signaling pathway. Knockdown of PKM2 by small interfering RNA reduced Hcy-induced CD4 + T cell IFN-γ secretion. Furthermore, we generated T cell-specific PKM2 knockout mice by crossing LckCre transgenic mice with PKM2 fl/fl mice and observed that Hcy-induced glycolysis and oxidative phosphorylation were both diminished in PKM2-deficient CD4 + T cells with reduced glucose and lipid metabolites, and subsequently reduced IFN-γ secretion. T cell-depleted apolipoprotein E-deficient (ApoE -/- ) mice adoptively transferred with PKM2-deficient CD4 + T cells, compared to mice transferred with control cells, showed significantly decreased HHcy-accelerated early atherosclerotic lesion formation. In conclusion, this work indicates that the PKM2-dependent glycolytic-lipogenic axis, a novel mechanism of metabolic regulation, is crucial for HHcy-induced CD4 + T cell activation to accelerate early atherosclerosis in ApoE -/- mice. Metabolic reprogramming is crucial for Hcy-induced CD4 + T cell inflammatory activation. Hcy activates

  15. CD4 T cell autophagy is integral to memory maintenance.

    Science.gov (United States)

    Murera, Diane; Arbogast, Florent; Arnold, Johan; Bouis, Delphine; Muller, Sylviane; Gros, Frédéric

    2018-04-13

    Studies of mice deficient for autophagy in T cells since thymic development, concluded that autophagy is integral to mature T cell homeostasis. Basal survival and functional impairments in vivo, limited the use of these models to delineate the role of autophagy during the immune response. We generated Atg5 f/f distal Lck (dLck)-cre mice, with deletion of autophagy only at a mature stage. In this model, autophagy deficiency impacts CD8 + T cell survival but has no influence on CD4 + T cell number and short-term activation. Moreover, autophagy in T cells is dispensable during early humoral response but critical for long-term antibody production. Autophagy in CD4 + T cells is required to transfer humoral memory as shown by injection of antigen-experienced cells in naive mice. We also observed a selection of autophagy-competent cells in the CD4 + T cell memory compartment. We performed in vitro differentiation of memory CD4 + T cells, to better characterize autophagy-deficient memory cells. We identified mitochondrial and lipid load defects in differentiated memory CD4 + T cells, together with a compromised survival, without any collapse of energy production. We then propose that memory CD4 + T cells rely on autophagy for their survival to regulate toxic effects of mitochondrial activity and lipid overload.

  16. Early determination of the congenital hypothyroidism by means of the cuantification of STH and T4 by radioimmunoassay method

    International Nuclear Information System (INIS)

    De Penados, R.C.

    1986-11-01

    It was investigated the advantages and disadvantages and conditions of working for the diagnosis of the congenital hypothyroidism by RIA, and its future implementation. It was determined concentration of neonatal STH and neonatal T4 in whole blood of 517 new borns, obtained by capilar punction and recollected in filter paper. 261 samples were found with levels of T4 between normal limits and STH between 0 and 12.5 u U/ml correspond to a normal thyroid function. 29 samples with normal T4 and STH above 30 u U/ml, correspond to a possible primary hypothyroidism. 171 samples with normal T4 and STH between 12.5 and 30 u U/ml were found. (Author)

  17. Increased thyroidal T4 to T3 conversion in autonomously functioning thyroid adenoma: from euthyroidism to thyrotoxicosis.

    LENUS (Irish Health Repository)

    Solter, M

    2012-01-31

    AIM: The aim was to investigate whether the intrathyroid conversion of T4 to T3 in autonomously functioning thyroid adenoma (AFTA) tissue could influence serum T3 levels and suppression of TSH, especially in patients with borderline thyroid function. PATIENTS AND METHODS: In ten patients with AFTA, thyroidal conversion of T4 to T3 was investigated in nodular and paranodular, TSH-suppressed tissue. All patients had normal serum T4 and suppressed TSH. Serum T3 was normal in six, and borderline or slightly increased in four. AFTA and paranodular tissues were surgically removed and frozen at -70 degrees C, then homogenized in a glass homogenizer, centrifuged at 100,000xg, and particulate fraction collected as a pellet. Analysis mixture consisted of thyroid enzyme suspension in 50 mumol\\/L TRIS buffer with 5 mumol DTT and 200 muL 1.3 mumol T4. Incubation was performed at 37 degrees C and the generation of T3 measured after 5, 10, 20 and 40 minutes respectively. RESULTS: T3 production (pmol\\/mg protein) was significantly higher in AFTA than in paranodular tissues (8.8 1.2\\/Mean +\\/- SE\\/vs. 1.8 +\\/- 0.2; p<0.01), and excessively high (9.8, 14.1, 14.2 and 15.0) in four patients with borderline or slightly supranormal serum T3. A significant correlation was found between serum T3 concentrations and T3 generation (T4 conversion) in AFTA tissues. CONCLUSION: Results suggest that increased thyroidal T4 to T3 conversion in AFTA tissue could be involved in an increased delivery of T3, increased serum T3 and suppressed serum TSH, particularly in patients with the disease evolving from euthyroid to an early hyperthyroid phase.

  18. Induction of CD4 suppressor T cells with anti-Leu-8 antibody

    International Nuclear Information System (INIS)

    Kanof, M.E.; Strober, W.; James, S.P.

    1987-01-01

    To characterize the conditions under which CD4 T cells suppress polyclonal immunoglobulin synthesis, we investigated the capacity of CD4 T cells that coexpress the surface antigen recognized by the monoclonal antibody anti-Leu-8 to mediate suppression. In an in vitro system devoid of CD8 T cells, CD4, Leu-8+ T cells suppressed pokeweed mitogen-induced immunoglobulin synthesis. Similarly, suppressor function was induced in unfractionated CD4 T cell populations after incubation with anti-Leu-8 antibody under cross-linking conditions. This induction of suppressor function by anti-Leu-8 antibody was not due to expansion of the CD4, Leu-8+ T cell population because CD4 T cells did not proliferate in response to anti-Leu-8 antibody. However, CD4, Leu-8+ T cell-mediated suppression was radiosensitive. Finally, CD4, Leu-8+ T cells do not inhibit immunoglobulin synthesis when T cell lymphokines were used in place of helper CD4 T cells (CD4, Leu-8- T cells), suggesting that CD4 T cell-mediated suppression occurs at the T cell level. We conclude that CD4 T cells can be induced to suppress immunoglobulin synthesis by modulation of the membrane antigen recognized by anti-Leu-8 antibody

  19. Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

    Science.gov (United States)

    Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

    2017-06-01

    CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  20. Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

    Science.gov (United States)

    Wang, Dongrui; Aguilar, Brenda; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Forman, Stephen J; Brown, Christine E

    2018-05-17

    Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

  1. NAD+ protects against EAE by regulating CD4+ T-cell differentiation

    Science.gov (United States)

    Tullius, Stefan G.; Biefer, Hector Rodriguez Cetina; Li, Suyan; Trachtenberg, Alexander J.; Edtinger, Karoline; Quante, Markus; Krenzien, Felix; Uehara, Hirofumi; Yang, Xiaoyong; Kissick, Haydn T.; Kuo, Winston P.; Ghiran, Ionita; de la Fuente, Miguel A.; Arredouani, Mohamed S.; Camacho, Virginia; Tigges, John C.; Toxavidis, Vasilis; El Fatimy, Rachid; Smith, Brian D.; Vasudevan, Anju; ElKhal, Abdallah

    2014-01-01

    CD4+ T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4+IFNγ+IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD+ regulates CD4+ T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD+, the frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4+ T-cell differentiation and demonstrate that NAD+ may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases. PMID:25290058

  2. Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

    Directory of Open Access Journals (Sweden)

    Nicholas Jones

    2017-11-01

    Full Text Available Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR and peptides presented by human leukocyte antigens (pHLA. The role of TCR–pHLA interactions in modulating T-cell metabolism is unknown. Here, for the first time, we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T-cell clones and altered peptide ligands, we demonstrate that binding affinity tunes the underlying metabolic shift. Overall, this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells.

  3. Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

    Science.gov (United States)

    Huang, Yung-Chin; Chu, Hsueh-Liang; Chen, Peng-Jen; Chang, Chia-Ching

    Thymosin beta 4 (T β4) is a 43-amino acid small peptide, has been demonstrated that it can promote cardiac repair, wound repair, tissue protection, and involve in the proliferation of blood cell precursor stem cells of bone marrow. Moreover, T β4 has been identified as a multifunction intrinsically disordered protein, which is lacking the stable tertiary structure. Owing to the small size and disordered character, the T β4 protein degrades rapidly and the storage condition is critical. Therefore, it is not easy to reveal its folding mechanism of native T β4. However, recombinant T β4 protein (rT β4), which fused with a 5-kDa peptide in its amino-terminal, is stable and possesses identical function of T β4. Therefore, rT β4 can be used to study its folding mechanism. By using over-critical folding process, stable folding intermediates of rT β4 can be obtained. Structure analysis of folding intermediates by synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies indicate that rT β4 is a random coli major protein and its hydrophobic region becomes compact gradually. Moreover, the rT β4 folding is a two state transition. Thermal denaturation analysis indicates that rT β4 lacks stable tertiary structure. These results indicated that rT β4, similar to T β4, is an intrinsically disordered protein. Research is supported by MOST, Taiwan. MOST 103-2112-M-009-011-MY3. Corresponding author: Chia-Ching Chang; ccchang01@faculty.nctu.edu.tw.

  4. CITOGENETICA DE HIBRIDOS ENTRE TURNERA GRANDIDENTATA (4x Y T. SUBULATA Y T. SCABRA (2x (TURNERACEAE

    Directory of Open Access Journals (Sweden)

    Aveliano Fernández

    1993-01-01

    Full Text Available Turnera subulata y T.scabra, 2n = 2x = 10, se cruzaron con T.grandidentata, 2n = 4x = 20, y los híbridos obtenidos se estudiaron citológicamente para determinar la relación entre estas especies. Todos los híbridos presentaron 2n = 3x = 15 y meiosis irregular. En T.subulata x T.grandidentata se hallo una asociación cromosómica media de 4,28 univalentes, 4,16 bivalentes y 0,73 trivalentes. T.scabra x T.grandidentata tuvieron una asociación cromosómica media de 4,53 univalentes, 4,42 bivalentes, 0,53 trivalentes y 0.03 cuadrivalents. El estudio citogenético de estos híbridos indica que estas tres especies tienen el mismo genoma básico. Las fórmulas genómicas Asu Asu para T.subulata, Asc Asc para T.scabra y AgAgArAr para T.grandidentata fueron propuestas en trabajos anteriores. Las asociaciones y las configuraciones que se encuentran en los híbridos analizados en éste estudio avalan las fórmulas genómicas propuestas.

  5. First experiences with the AMERLEX-MAB FREE T4 assay

    International Nuclear Information System (INIS)

    Nijhof, W.A.; Penders, T.J.

    1989-01-01

    The new Amerlex-MAB FT 4 is a quick direct free T 4 assay with good reproducability. The correlation between the Amerlex-MAB FT 4 and the free T 4 of Byk is good. In the non-thyreoidal illness patient group no deviation for the values were found. Amerlex-MAB FT 4 is cheaper, because no total T4 has to be measured. More research has to be done for special patient sera. Disturbing influences as free fatty acids, heparin and auto-antibodies have to be checked. (R.B.). 3 refs.; 3 figs.; 4 tabs

  6. Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

    Science.gov (United States)

    Katri, Patricia; Ruan, Shigui

    2004-11-01

    Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

  7. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    Science.gov (United States)

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  8. Work Limitations 4 Years After Mild Traumatic Brain Injury: A Cohort Study.

    Science.gov (United States)

    Theadom, Alice; Barker-Collo, Suzanne; Jones, Kelly; Kahan, Michael; Te Ao, Braden; McPherson, Kathryn; Starkey, Nicola; Feigin, Valery

    2017-08-01

    To explore employment status, work limitations, and productivity loss after mild traumatic brain injury (TBI). Inception cohort study over 4 years. General community. Adults (N=245; >16y at the time of injury) who experienced a mild TBI and who were employed prior to their injury. Not applicable. Details of the injury, demographic information, and preinjury employment status were collected from medical records and self-report. Symptoms and mood were assessed 1 month postinjury using the Rivermead Post-Concussion Symptom Questionnaire and the Hospital Anxiety and Depression Scale. Postinjury employment status and work productivity were assessed 4 years postinjury using the Work Limitations Questionnaire. Four years after mild TBI, 17.3% of participants had exited the workforce (other than for reasons of retirement or to study) or had reduced their working hours compared with preinjury. A further 15.5% reported experiencing limitations at work because of their injury. Average work productivity loss was 3.6%. The symptom of taking longer to think 1 month postinjury significantly predicted work productivity loss 4 years later (β=.47, t=3.79, P≤.001). Although changes in employment status and difficulties at work are likely over time, the results indicate increased unemployment rates, work limitations, and productivity loss in the longer term after a mild TBI. Identification of cognitive difficulties 1 month after TBI in working aged adults and subsequent interventions to address these difficulties are required to facilitate work productivity. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  9. The epidemiologic study: the serum levels of TSH, T4, T3 and autoantibodies in the Polish population

    International Nuclear Information System (INIS)

    Gardas, A.

    1991-01-01

    In 1986-1990 epidemiologic studies on the thyroid diseased frequency in the Polish population were undertaken. During this studies the serum levels of TSH, T 4 , T 3 and autoantibodies were estimated in more then 30 thousand people. TSH was estimated in 30749, T 4 in 30928, T 3 in 30621 and autoantibodies in 31265 randomly chosen people in 5 districts. We have arbitrarily established the normal range for TSH to be between 0.4-3.8 μIU/ml, for T 4 4.4-12.5 μg and for T 3 0.9-1.95 ng/ml. The tested group has been divide in 4 subgroup: girls and boys from 1 to 15 years of age of the Chernobyl accident, men and women from 15 to 50 years of age at the date of the accident. TSH values in the normal range were found in 85 to 92% of the tested population, depending on the subgroup. T 4 vales in the normal range were found in 85 to 92% of the tested groups. T 3 vales in the normal range were found in 86 to 93% of the tested groups. The absence on any kind of autoantibodies was established in 89.7% of the tested population. TSH values was above the normal range (above 3.8 μIU/ml) in 3.4% of boys, 4.3% girls, 3.2% men and 3.8% women. TSH vales below the normal range (less the 0.4 μIU/ml) were found in 4.3% boys, 5% girls, 10% men and 11.2% women. T 4 values above the normal range (higher then 12.5 μg%) were found in 12.9% boys, 12.6% girls, 4.6% men and 5.9% women. T 4 vales below the normal range (less then 4.4 μg%) were detected in 0.9% boys, 1.4% girls, 2.4% men and 2.0% women. T 3 values higher then 1.95 ng/ml were found in 10.8% of boys, 11.5% girls, 2.6% men and 3.5% women. The percentage of values above of below the arbitrarily chosen normal range depends on the age and sex group. (author). 5 refs, 4 tabs

  10. Incorporation of T4 bacteriophage in electrospun fibres.

    Science.gov (United States)

    Korehei, R; Kadla, J

    2013-05-01

    Antibacterial food packaging materials, such as bacteriophage-activated electrospun fibrous mats, may address concerns triggered by waves of bacterial food contamination. To address this, we investigated several efficient methods for incorporating T4 bacteriophage into electrospun fibrous mats. The incorporation of T4 bacteriophage using simple suspension electrospinning led to more than five orders of magnitude decrease in bacteriophage activity. To better maintain bacteriophage viability, emulsion electrospinning was developed where the T4 bacteriophage was pre-encapsulated in an alginate reservoir via an emulsification process and subsequently electrospun into fibres. This resulted in an increase in bacteriophage viability, but there was still two orders of magnitude drop in activity. Using a coaxial electrospinning process, full bacteriophage activity could be maintained. In this process, a core/shell fibre structure was formed with the T4 bacteriophage being directly incorporated into the fibre core. The core/shell fibre encapsulated bacteriophage exhibited full bacteriophage viability after storing for several weeks at +4°C. Coaxial electrospinning was shown to be capable of encapsulating bacteriophages with high loading capacity, high viability and long storage time. These results are significant in the context of controlling and preventing bacterial infections in perishable foods during storage. © 2013 The Society for Applied Microbiology.

  11. Long-baseline neutrino oscillation experiments

    International Nuclear Information System (INIS)

    Crane, D.; Goodman, M.

    1994-01-01

    There is no unambiguous definition for long baseline neutrino oscillation experiments. The term is generally used for accelerator neutrino oscillation experiments which are sensitive to Δm 2 2 , and for which the detector is not on the accelerator site. The Snowmass N2L working group met to discuss the issues facing such experiments. The Fermilab Program Advisory Committee adopted several recommendations concerning the Fermilab neutrino program at their Aspen meeting immediately prior to the Snowmass Workshop. This heightened the attention for the proposals to use Fermilab for a long-baseline neutrino experiment at the workshop. The plan for a neutrino oscillation program at Brookhaven was also thoroughly discussed. Opportunities at CERN were considered, particularly the use of detectors at the Gran Sasso laboratory. The idea to build a neutrino beam from KEK towards Superkamiokande was not discussed at the Snowmass meeting, but there has been considerable development of this idea since then. Brookhaven and KEK would use low energy neutrino beams, while FNAL and CERN would plan have medium energy beams. This report will summarize a few topics common to LBL proposals and attempt to give a snapshot of where things stand in this fast developing field

  12. Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

    Science.gov (United States)

    Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban

    2017-11-17

    Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

  13. Evaluación de la capacidad de reconocimiento de los anticuerpos monoclonales conjugados: IOR T3, T4 Y T8 Assessment of recognition ability of conjugate monoclonal antibodies: IOR T3, T4 and T8

    Directory of Open Access Journals (Sweden)

    Liliana Pérez Toledo

    2000-04-01

    Full Text Available En la infección por VIH la evaluación secuencial de los valores de linfocitos CD3, CD4 y CD8 aportan información para el establecimiento del estado clínico y el pronóstico de los pacientes. Disponer de reactivos óptimos, producidos en nuestro país, para su uso en citometría de flujo, implica un ahorro sin que se afecte la calidad. El Laboratorio Diagnóstico del Instituto de Medicina Tropical (IPK correlacionó el porcentaje de linfocitos reconocidos por los anticuerpos monoclonales (AcMs conjugados producidos por el Centro de Inmunología Molecular (CIM (CIMAB SA, La Habana, Cuba [ior T3, T4 y T8] frente a sus similares de la casa comercial DAKO AG (Dinamarca, en muestras de pacientes en diferentes estadios de la enfermedad, tomados aleatoriamente. Los resultados del coeficiente de correlación para cada AcM utilizando una regresión simple, fueron los siguientes: CD3=0,932; CD4=0,986; CD8=0,958. Con este estudio se demostró que los AcMs conjugados de la serie ior (CIMAB SA se comportan, en cuanto a porcentaje de reconocimiento, de forma similar a los de la casa comercial DAKO, lo que posibilita el diagnóstico y monitoreo de los pacientes VIH/SIDA cubanosIn VIH infection, sequential assessment of CD3, CD4, and CD8 lymphocytes values, provide information to stablishment of clinical status and prognosis of patients. Availability of optimal reagents of national manufacture to use in flow cytometry, means a saving without to affect quality. Diagnostic Laboratory of "Pedro Kourí" Institute of Tropical Medicine (IPK to correlates percentage of lymphocytes recognized by conjugate monoclonal antibodies (MAB, produced by Center of Molecular Immunology (CMI (CIMAB S.A. Havana, Cuba [ior T3, T4, and T8] versus homologous of DAKO AG commercial firm (Denmark in randomized patient´s samples in different diseases stage. Results of correlation coefficient to each MAB, using single regression were as follow: CD3=0,932; CD4=0,986; CD8=0,958. This

  14. Working Group Report: WIMP Dark Matter Direct Detection

    Energy Technology Data Exchange (ETDEWEB)

    Cushman, P.; Galbiati, C.; McKinsey, D. N.; Robertson, H.; Tait, T. M.P.

    2013-10-30

    As part of the Snowmass process, the Cosmic Frontier WIMP Direct Detection subgroup (CF1) has drawn on input from the Cosmic Frontier and the broader Particle Physics community to produce this document. The charge to CF1 was (a) to summarize the current status and projected sensitivity of WIMP direct detection experiments worldwide, (b) motivate WIMP dark matter searches over a broad parameter space by examining a spectrum of WIMP models, (c) establish a community consensus on the type of experimental program required to explore that parameter space, and (d) identify the common infrastructure required to practically meet those goals.

  15. Working Group Report: WIMP Dark Matter Direct Detection

    International Nuclear Information System (INIS)

    Cushman, P.; Galbiati, C.; McKinsey, D. N.; Robertson, H.; Tait, T. M.P.

    2013-01-01

    As part of the Snowmass process, the Cosmic Frontier WIMP Direct Detection subgroup (CF1) has drawn on input from the Cosmic Frontier and the broader Particle Physics community to produce this document. The charge to CF1 was (a) to summarize the current status and projected sensitivity of WIMP direct detection experiments worldwide, (b) motivate WIMP dark matter searches over a broad parameter space by examining a spectrum of WIMP models, (c) establish a community consensus on the type of experimental program required to explore that parameter space, and (d) identify the common infrastructure required to practically meet those goals.

  16. Non-water-suppressed 1 H FID-MRSI at 3T and 9.4T.

    Science.gov (United States)

    Chang, Paul; Nassirpour, Sahar; Avdievitch, Nikolai; Henning, Anke

    2018-08-01

    This study investigates metabolite concentrations using metabolite-cycled 1 H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1 H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, ∼0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. We showed the first implementation of non-water-suppressed metabolite-cycled 1 H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed. Magn Reson Med 80:442-451, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society

  17. Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

    Science.gov (United States)

    Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

    2013-09-01

    Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

  18. Substitution of 125-I-T3, 125-I-T4 and 125-I-TSH produced in the ININ, in commercial boxes for radioimmunoessay; Substitucion de 125-I-T3, 125-I-T4 y 125-I-TSH producidas en el ININ, en estuches comerciales para radioinmunoanalisis

    Energy Technology Data Exchange (ETDEWEB)

    Delgado S, B; Zambrano A, F; Lavalley E, C; Ferro F, G; Lezama C, J

    1991-03-15

    Due to the half, relatively short life, of the I-125 used in the radioinmunoanalisis (he/she LAUGHS) of hormones realcionadas with the thyroid, frequently it is observed that they are the other reagents of commercial cases without using, reason for the one which you piede the possibility to use in their entirety statements kits for the CREEK, what causes lost economic and another type of deficiencies. Presently work the results are presented obtained on the characteristics of quality of commercial stuches for the CREEK of hormones of the thyroid profile (T3, T4 and TSH), after substituting to the different radiotrazadores in this cases. The marcaje of the hormones with I-125 was made by means of the method of the cloramina T with 25 seconds of reaction for each hormone, purifying the T3 and the T4 for cromatografia liquidates of high efficiency and to the TSH for cromatografia of likeness in a column of cellulose microcristalina of 6 x 0.8 cm. the substitution of the radiotrazador is made in the commercial cases and the protocol was continued proposed by the makers, giving a coefficient of correlation of -0-997, as a result after the comparison of the straight line among the cases without and with substitution of the radiotrazador; besides certain parameters of quality of the such rehearsals as: the maximum unions (50%+-5) and inespecifica (<5%), slope of the straight line (-2.1 + - 0.2), and other coming from the use of samples of control of quality. We can conclude that at the moment we have in the ININ radiotrazadores of T3, T4 and TSH of good quality, like to be substituted in commercial cases and to use this way to the maximum these games of reagents that are so expensive. (Author)

  19. Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells.

    Science.gov (United States)

    Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J

    2013-01-01

    After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show down regulation of mucosal CD4+ T cell proliferation, IL-2 production and cell surface marker expression of mucosal CD4+ T cells moving towards suppressive-type. Acute burn-injury lead to up-regulation of regulatory marker (CD25+), down regulation of adhesion (CD62L, CD11a) and homing receptor (CD49d) expression, and up-regulation of negative co-stimulatory (CTLA-4) molecule. Moreover, CD4+CD25+ T cells of intestinal origin showed resistance to spontaneous as well as induced apoptosis that may contribute to suppression of effector CD4+ T cells. Furthermore, gut CD4+CD25+ T cells obtained from burn-injured animals were able to down-regulate naïve CD4+ T cell proliferation following adoptive transfer of burn-injured CD4+CD25+ T cells into sham control animals, without any significant effect on cell surface activation markers. Together, these data demonstrate that the intestinal CD4+ T cells evolve a strategy to promote suppressive CD4+ T cell effector responses, as evidenced by enhanced CD4+CD25+ T cells, up-regulated CTLA-4 expression, reduced IL-2 production, tendency towards diminished apoptosis of suppressive CD4+ T cells, and thus lose their natural ability to regulate immune homeostasis following acute burn-injury and prevent immune paralysis.

  20. The peripheral conversion of thyroxine (T4) into triiodothyronine (T3) and reverse triiodothyronine (rT3)

    International Nuclear Information System (INIS)

    Wiersinga, W.M.

    1979-01-01

    The aim of this study was to delineate several physiological, pathological and pharmacological factors involved in the peripheral conversion of thyroxine (T 4 ), using radioimmunoassay. The determination of normal values of these tests under basal circumstances and after stimulation with thyrotropin-releasing-hormone is presented, and some physiological factors which may modulate the conversion of T 4 are discussed. Results are presented of the thyroid function tests in patients with thyroid disease and with acute non-thyroidal diseases. (Auth.)

  1. Blood Pressure Medicines Don’t Work If People Don’t Take Them PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the September 2016 CDC Vital Signs report. Blood pressure medicines don’t work if people don’t take them. Learn how health care systems can work with patients to make taking medicines easier.

  2. Structure and assembly of bacteriophage T4 head

    Directory of Open Access Journals (Sweden)

    Black Lindsay W

    2010-12-01

    Full Text Available Abstract The bacteriophage T4 capsid is an elongated icosahedron, 120 nm long and 86 nm wide, and is built with three essential proteins; gp23*, which forms the hexagonal capsid lattice, gp24*, which forms pentamers at eleven of the twelve vertices, and gp20, which forms the unique dodecameric portal vertex through which DNA enters during packaging and exits during infection. The past twenty years of research has greatly elevated the understanding of phage T4 head assembly and DNA packaging. The atomic structure of gp24 has been determined. A structural model built for gp23 using its similarity to gp24 showed that the phage T4 major capsid protein has the same fold as that found in phage HK97 and several other icosahedral bacteriophages. Folding of gp23 requires the assistance of two chaperones, the E. coli chaperone GroEL and the phage coded gp23-specific chaperone, gp31. The capsid also contains two non-essential outer capsid proteins, Hoc and Soc, which decorate the capsid surface. The structure of Soc shows two capsid binding sites which, through binding to adjacent gp23 subunits, reinforce the capsid structure. Hoc and Soc have been extensively used in bipartite peptide display libraries and to display pathogen antigens including those from HIV, Neisseria meningitides, Bacillus anthracis, and FMDV. The structure of Ip1*, one of the components of the core, has been determined, which provided insights on how IPs protect T4 genome against the E. coli nucleases that degrade hydroxymethylated and glycosylated T4 DNA. Extensive mutagenesis combined with the atomic structures of the DNA packaging/terminase proteins gp16 and gp17 elucidated the ATPase and nuclease functional motifs involved in DNA translocation and headful DNA cutting. Cryo-EM structure of the T4 packaging machine showed a pentameric motor assembled with gp17 subunits on the portal vertex. Single molecule optical tweezers and fluorescence studies showed that the T4 motor packages

  3. Sequence organization and control of transcription in the bacteriophage T4 tRNA region.

    Science.gov (United States)

    Broida, J; Abelson, J

    1985-10-05

    Bacteriophage T4 contains genes for eight transfer RNAs and two stable RNAs of unknown function. These are found in two clusters at 70 X 10(3) base-pairs on the T4 genetic map. To understand the control of transcription in this region we have completed the sequencing of 5000 base-pairs in this region. The sequence contains a part of gene 3, gene 1, gene 57, internal protein I, the tRNA genes and five open reading frames which most likely code for heretofore unidentified proteins. We have used subclones of the region to investigate the kinetics of transcription in vivo. The results show that transcription in this region consists of overlapping early, middle and late transcripts. Transcription is directed from two early promoters, one or two middle promoters and perhaps two late promoters. This region contains all of the features that are seen in T4 transcription and as such is a good place to study the phenomenon in more detail.

  4. Total glucosides of paeony induces regulatory CD4(+)CD25(+) T cells by increasing Foxp3 demethylation in lupus CD4(+) T cells.

    Science.gov (United States)

    Zhao, Ming; Liang, Gong-ping; Tang, Mei-ni; Luo, Shuang-yan; Zhang, Jing; Cheng, Wen-jing; Chan, Tak-mao; Lu, Qian-jin

    2012-05-01

    Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our results also showed that IFN-γ and IL-2 expression was enhanced in TGP-treated lupus CD4(+) T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3

    Directory of Open Access Journals (Sweden)

    Yuta Kobayashi, MS

    2016-10-01

    Conclusions: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

  6. Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

    Science.gov (United States)

    Sharma, Sonia; Grandvaux, Nathalie; Mamane, Yael; Genin, Pierre; Azimi, Nazli; Waldmann, Thomas; Hiscott, John

    2002-09-15

    IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

  7. T4 bacteriophage conjugated magnetic particles for E. coli capturing: Influence of bacteriophage loading, temperature and tryptone.

    Science.gov (United States)

    Liana, Ayu Ekajayanthi; Marquis, Christopher P; Gunawan, Cindy; Gooding, J Justin; Amal, Rose

    2017-03-01

    This work demonstrates the use of bacteriophage conjugated magnetic particles (Fe 3 O 4 ) for the rapid capturing and isolation of Escherichia coli. The investigation of T4 bacteriophage adsorption to silane functionalised Fe 3 O 4 with amine (NH 2 ), carboxylic (COOH) and methyl (CH 3 ) surface functional groups reveals the domination of net electrostatic and hydrophobic interactions in governing bacteriophage adsorption. The bare Fe 3 O 4 and Fe 3 O 4 -NH 2 with high T4 loading captured 3-fold more E. coli (∼70% capturing efficiency) compared to the low loading T4 on Fe 3 O 4 -COOH, suggesting the significance of T4 loading in E. coli capturing efficiency. Importantly, it is further revealed that E. coli capture is highly dependent on the incubation temperature and the presence of tryptone in the media. Effective E. coli capturing only occurs at 37°C in tryptone-containing media with the absence of either conditions resulted in poor bacteria capture. The incubation temperature dictates the capturing ability of Fe 3 O 4 /T4, whereby T4 and E. coli need to establish an irreversible binding that occurred at 37°C. The presence of tryptophan-rich tryptone in the suspending media was also critical, as shown by a 3-fold increase in E. coli capture efficiency of Fe 3 O 4 /T4 in tryptone-containing media compared to that in tryptone-free media. This highlights for the first time that successful bacteria capturing requires not only an optimum tailoring of the particle's surface physicochemical properties for favourable bacteriophage loading, but also an in-depth understanding of how factors, such as temperature and solution chemistry influence the subsequent bacteriophage-bacteria interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Assembly and dynamics of the bacteriophage T4 homologous recombination machinery

    Directory of Open Access Journals (Sweden)

    Morrical Scott W

    2010-12-01

    Full Text Available Abstract Homologous recombination (HR, a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR. T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms.

  9. Clinical and evolutive aspects of nasopharyngeal T4 NO

    International Nuclear Information System (INIS)

    Maalej, M.; Bouaouina, N.; Benna, F.; Frikha, H.; Jallouli, M.; Ellouze, R.; Ben Romdhane, K.; Cammoun, M.; Ben Attia, R.; Daoud, J.

    1995-01-01

    Nasopharyngeal carcinoma (NPC) is the primary cancer of the head and neck localizations in the Salah Azaiz Institute (Tunisia). From 1970 to 1987, 80 patients with histologically proven T4 NO NPC, were treated with exclusive radiation (70-75 Gy to the primary lesion and 50-55 Gy to cervical lymph nodes). The T4 NO represents 7% of all NPC and 16% of the T4 treated in our Institute. Ninety percent of the patients are over 20 years old with a mean age of 52 years. The sex-ration was 4: 1. Extension to the brain was observed in 55% of the cases. Local control was 70% at 2 months after the end of irradiation. The actuarial survival at 5 years was 47%. Distant metastasis represent 13% (30% for all NPC). The main failure of treatment was local recurrence. The T4 NO is probably a particular entity concerning the age, the response to radiotherapy and the low rate of distant metastasis. (authors). 18 refs., 5 figs

  10. HUBUNGAN KANDUNGAN KLOR SERUM DENGAN HORMON T3/T4 PADA ANAK SEKOLAH DI DAERAH GONDOK ENDEMIK

    Directory of Open Access Journals (Sweden)

    Sukati Saidin

    2012-11-01

    Full Text Available ASSOCIATION OF SERUM CHLOR CONTENT WITH T3/T4 HORMONEIN SCHOOL CHILDREN IN IODINE DEFICIENCY REGION.Background: The National Mapping Survey of IDD (1998 found that 7% of sub districts In Indonesia was regarded as severe endemic goitre area (TGR>30%. The high TGR prevalence, beside as a result of low iodized salt consumption (< 30 ppm, It was assumed as the effect of exposure of goitrogenic agent such as chlorine. Based on observation in Karawang sub district showed people had food habit to consume fish contaminated by insecticide used for killing milk fish predator or salted fish which had also contaminated by insecticide used during process of fish drying. Insecticide raw material consists of chlorine which can not be broken by heat or oxidation. Previous study by Gaitan E. (1986 found that chlorine component could inhibit iodine metabolism to form mono and di-iodotyrosine as precursor of T3 and T4 hormones.Objectives: The aim of this study was to find an association of serum chlorine as a reflection of chlorine consumption from daily food with T3 and T4 hormone.Methods: Research design was case control. Study was conducted in Karawang district, West Java. The subject were elementary school children in the fourth, fifth and sixth grades with positive goitre at grade I and II by palpation. Sample size was 140 children divided into two groups, case group (70 children and control group (70 children. Main data collected was chlorine consumption from daily food, serum chlorine, serum T3 and T4 hormones as well as anthropometries.Results: The result showed that chlorine consumption from food was relatively greater in case group (135.9 ugr/day than in control group (129.9 ug/day but statistically it was not significant. Serum chlorine content in case group (1 14.8 mmol/L was significantly higher than in control group (102.1 mmol/L. Serum T4 hormone in case group (7.3 ug/dl was significantly lower than in control group (9.5 ug/dl. Serum T3 hormone in

  11. Family of autocatalytic group I introns in bacteriophage T4

    International Nuclear Information System (INIS)

    Shub, D.A.; Xu, M.Q.; Gott, J.M.; Zeeh, A.; Wilson, L.D.

    1987-01-01

    The discovery of an intron in phage T4 encouraged the authors to look for additional group I introns in the T4 genome. Further examples would permit sequence and structural comparisons that might lend insight into their evolutionary origin. Additionally, they hoped that their locations within the T4 genome would infer a possible regulatory function in prokaryotic gene expression. They took advantage of the fact that, since G is added to the 5' end of the intron, autocatalytic group I introns could be specifically labeled in vitro for use as probes for DNA blotting experiments. If Group I introns were in more than just the td gene, multiple RNA species should be labeled when total RNA is extracted from T4-infected cells and incubated with [α- 32 P]GTP in vitro. When used as a probe for a Southern blot of T4 DNA, this RNA should hybridize to several DNA bands

  12. CD4+ and CD8+ T cell activation are associated with HIV DNA in resting CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Leslie R Cockerham

    Full Text Available The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1 in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.

  13. Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids.

    Science.gov (United States)

    Lin, Shi-lei; Wang, Cong-wu; Tan, Si-ran; Liang, Yang; Yao, Hai-dong; Zhang, Zi-wei; Xu, Shi-wen

    2014-12-01

    Selenium (Se) influences the metabolism of thyroid hormones in mammals. However, the role of Se deficiency in the regulation of thyroid hormones in chickens is not well known. In the present study, we examined the levels of thyroidal triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA expression levels of 25 selenoproteins in chicken thyroids. Then, principal component analysis (PCA) was performed to analyze the relationships between the selenoproteins. The results indicated that Se deficiency influenced the conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition, the mRNA expression levels of the selenoproteins were generally decreased by Se deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2, Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u (Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which indicated that they may play similar roles in the metabolism of thyroid hormones. The results showed that Se deficiency inhibited the conversion of T4 to T3 and decreased the levels of the crucial metabolic enzymes of the thyroid hormones, Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins (Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency may indirectly limit the conversion of T4 to T3 in chicken thyroids. The information presented in this study is helpful to understand the role of Se in the thyroid function of chickens.

  14. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

    DEFF Research Database (Denmark)

    Nygaard, Birte

    2012-01-01

    . Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues...

  15. pVT-Second Virial Coefficients B(T ), Viscosity η(T ), and Self-Diffusion ρD(T) of the Gases: BF3, CF4, SiF4, CCl4, SiCl4, SF6, MoF6, WF6, UF6, C(CH3)4, and Si(CH3)4 Determined by Means of an Isotropic Temperature-Dependent Potential

    Science.gov (United States)

    Zarkova, L.; Hohm, U.

    2002-03-01

    We present results on self-consistent calculations of second pVT-virial coefficients B(T), viscosity data η(T), and diffusion coefficients ρD(T) for eleven heavy globular gases: boron trifluoride (BF3), carbon tetrafluoride (CF4), silicon tetrafluoride (SiF4), carbon tetrachloride (CCl4), silicon tetrachloride (SiCl4), sulfur hexafluoride (SF6), molybdenum hexafluoride (MoF6), tungsten hexafluoride (WF6), uranium hexafluoride (UF6), tetramethyl methane (C(CH3)4, TMM), and tetramethyl silane (Si(CH3)4, TMS). The calculations are performed mainly in the temperature range between 200 and 900 K by means of isotropic n-6 potentials with temperature-dependent separation rm(T) and potential well depth ɛ(T). The potential parameters at T=0 K (ɛ, rm, n) and the enlargement of the first level radii δ are obtained solving an ill-posed problem of minimizing the squared deviations between experimental and calculated values normalized to their relative experimental error. The temperature dependence of the potential is obtained as a result of the influence of vibrational excitation on binary interactions. This concept of the isotropic temperature-dependent potential (ITDP) is presented in detail where gaseous SF6 will serve as an example. The ITDP is subsequently applied to all other gases. This approach and the main part of the results presented here have already been published during 1996-2000. However, in some cases the data are upgraded due to the recently improved software (CF4, SF6) and newly found experimental data (CF4, SiF4, CCl4, SF6).

  16. Thyroid hormone uptake and T4 derived T3 formation in different skeletal muscle types of normal and hyperthyroid rats

    International Nuclear Information System (INIS)

    Hardeveld, C. van; Kassenaar, A.A.H.

    1978-01-01

    In this study hind-limb perfusion was used to investigate conversion of T 4 to T 3 in skeletal muscle tissue. For this purpose the rats were depleted of thyroid hormones by thyroid ablation with 0.75 mCi 131 I and were perfused 2 weeks later, when the skeletal muscle tissue consumed oxygen at a normal rate due to one subcutaneous dose of 10 μg T 3 /100 g b. w. 3 days before the perfusion experiments were started. T 4 * of high specific activity (> 2000 μCi/μg) was added to the perfusate. In the muscle (mixed type) a mean T 4T 3 conversion of 2% (range 0.5-3.9) was found after 120 min of perfusion. T 3 generation from T 4 in skeletal muscle did not correspond with T 3 muscle uptake. This observation makes a significant overestimation of T 3 by selective uptake of a small contamination of T 3 * in the T 4 * preparation highly improbable. In red muscle the T 4 and T 3 uptake was about 50 % higher than in white muscle. The observed Tetracsup(c) and T 3 sup(c) were significantly higher in red than in white muscle. The uptake of thyroid hormones by both muscle types was not changed in hyperthyroid rats. The Tetrac and T 3 formation from T 4 , however, was increased in red muscles of hyperthyroid rats. The results show that thyroid hormone metabolism can vary markedly depending upon the type of muscle studied and they present a basis for a better understanding of clinical and biochemical evidence for a different susceptibility of red and white muscle fibers to thyroid hormones. (Abbreviations: *= 125 I; **= 131 I; T 3 sup(c)=T 4 derived T 3 ; Tetracsup(c)=T 4 derived Tetrac) (author)

  17. The development of T3-RIA, T4-RIA and TSH-IRMA for in vitro testing of thyroid function

    International Nuclear Information System (INIS)

    Borza, V.; Neacsu, G.; Chariton, Despina

    1998-01-01

    Thyroxine (T 4 ) and triiodothyronine (T 3 ) are two principal thyroid hormones; the release of this hormones and control of different stages of their synthesis are performed by thyrotropin (TSH), secreted by pituitary gland. Also, T 3 and T 4 exert negative feed-back on the pituitary, inhibiting the release of TSH. The measurement of T 3 , T 4 content in un-extracted serum, correlated with TSH values are useful results for investigating the pituitary-thyroid axis. This paper describes radioimmunological procedures for the measurement of T 3 and T 4 using as separation method of the bound and free radiolabeled antigen, the precipitation of antigen-antibody complex by polyethyleneglycol (PEG). Antisera against T 3 , T 4 were produced by immunizing sheep with conjugates of the hormones and bovine albumin; T 3 and T 4 standards were made in horse serum free of these hormones. Binding of T 3 and T 4 to TBG in serum was inhibited by addition of 8-aniline-1-naphthalene-sulfonic acid (ANS). The separation of antigen-antibody complex was carried out using 25.5% PEG 6000. In order to develop a simple T 3 solid phase radioimmunoassay, in this paper the immobilization of anti-T 3 antibodies on polystyrene tubes is presented. The best results were obtained with an exposure time of anti-T 3 antibodies (diluted in buffer solution, pH 8.4-8.6) of 40 h at 4 o C. Also, in this study the preparation of 125 I labeled monoclonal antibody (Mab)-anti-TSH is described, which will be used as a component of a TSH-IRMA kit; this kit is to be realized in our department. 125 I - Mab anti-TSH has the following characteristics: specific activity = 20 - 24 μCi/μg and radioactive concentration ≅ 25 μCi/ml; also, the immunological properties of tracer were verified. The major results of this activity is that the total dependence on important kits will be eliminated and also, the costs will be reduced. (authors)

  18. A review of MAAP4 code structure and core T/H model

    International Nuclear Information System (INIS)

    Song, Yong Mann; Park, Soo Yong

    1998-03-01

    The modular accident analysis program (MAAP) version 4 is a computer code that can simulate the response of LWR plants during severe accident sequences and includes models for all of the important phenomena which might occur during accident sequences. In this report, MAAP4 code structure and core thermal hydraulic (T/H) model which models the T/H behavior of the reactor core and the response of core components during all accident phases involving degraded cores are specifically reviewed and then reorganized. This reorganization is performed via getting the related models together under each topic whose contents and order are same with other two reports for MELCOR and SCDAP/RELAP5 to be simultaneously published. Major purpose of the report is to provide information about the characteristics of MAAP4 core T/H models for an integrated severe accident computer code development being performed under the one of on-going mid/long-term nuclear developing project. The basic characteristics of the new integrated severe accident code includes: 1) Flexible simulation capability of primary side, secondary side, and the containment under severe accident conditions, 2) Detailed plant simulation, 3) Convenient user-interfaces, 4) Highly modularization for easy maintenance/improvement, and 5) State-of-the-art model selection. In conclusion, MAAP4 code has appeared to be superior for 3) and 4) items but to be somewhat inferior for 1) and 2) items. For item 5), more efforts should be made in the future to compare separated models in detail with not only other codes but also recent world-wide work. (author). 17 refs., 1 tab., 12 figs

  19. Preparation of quality control samples for thyroid hormones T3 and T4 in radioimmunoassay techniques

    International Nuclear Information System (INIS)

    Ahmed, F.O.A.

    2006-03-01

    Today, the radioimmunoassay becomes one of the best techniques for quantitative analysis of very low concentration of different substances. RIA is being widely used in medical and research laboratories. To maintain high specificity and accuracy in RIA and other related techniques the quality controls must be introduced. In this dissertation quality control samples for thyroid hormones (Triiodothyronine T3 and Thyroxin T4), using RIA techniques. Ready made chinese T4, T3 RIA kits were used. IAEA statistical package were selected.(Author)

  20. Fast algorithms for coordinate processors in Galois field for multiplicity t = 4.5 and t > 5

    International Nuclear Information System (INIS)

    Nikityuk, N.M.

    1989-01-01

    Fast algorithms for solving the coordinate equations for special-purpose processors at multiplicity t = 4.5 and t > 5 are described. Block diagrams of coordinate processor for t 4 in Galois field GF(2 m ) is presented which is solved by a table method. Economical algorithms for solving the coordinate equations by serial methods at t > 5 are described. The algorithms and devices proposed could be applied when creating fast processors in high energy physics spectrometers. 9 refs.; 3 figs

  1. The Effects of Theta and Gamma tACS on Working Memory and Electrophysiology

    Directory of Open Access Journals (Sweden)

    Anja Pahor

    2018-01-01

    Full Text Available A single blind sham-controlled study was conducted to explore the effects of theta and gamma transcranial alternating current stimulation (tACS on offline performance on working memory tasks. In order to systematically investigate how specific parameters of tACS affect working memory, we manipulated the frequency of stimulation (theta frequency vs. gamma frequency, the type of task (n-back vs. change detection task and the content of the tasks (verbal vs. figural stimuli. A repeated measures design was used that consisted of three sessions: theta tACS, gamma tACS and sham tACS. In total, four experiments were conducted which differed only with respect to placement of tACS electrodes (bilateral frontal, bilateral parietal, left fronto-parietal and right-fronto parietal. Healthy female students (N = 72 were randomly assigned to one of these groups, hence we were able to assess the efficacy of theta and gamma tACS applied over different brain areas, contrasted against sham stimulation. The pre-post/sham resting electroencephalogram (EEG analysis showed that theta tACS significantly affected theta amplitude, whereas gamma tACS had no significant effect on EEG amplitude in any of the frequency bands of interest. Gamma tACS did not significantly affect working memory performance compared to sham, and theta tACS led to inconsistent changes in performance on the n-back tasks. Active theta tACS significantly affected P3 amplitude and latency during performance on the n-back tasks in the bilateral parietal and right-fronto parietal protocols.

  2. Basic and clinical evaluation of thyroxine radioimmunoassay kit. I. T-4 RIA kit

    Energy Technology Data Exchange (ETDEWEB)

    Bunko, H; Hisada, K [Kanazawa Univ. (Japan). Hospital

    1976-02-01

    The T/sub 4/ RIA kit is based on single antibody radioimmunoassay and utilizes a resin-sponge to separate free T/sub 4/-/sup 125/I from the incubation mixture. The use of the sodium salt of trichloroacetic acid (TBG inhibitor) permits direct radioimmunoassay of T/sub 4/ without a tedious extraction procedure. The T/sub 4/ RIA kit needs only 0.05 ml of patient serum and one hour of incubation to measure T/sub 4/. The TBG inhibitior was equivalent to 5.1 ..mu..g% of T/sub 4/ in displacing radioactive T/sub 4/ from TBG in a CPBA(Res-O-Mat T/sub 4/) system, and the TBG inhibitor volume of 0.5 ml (ten times of serum) was needed to measure a high T/sub 4/ concentration serum. The change of incubation temperature was more affected on the standard curve than that of incubation time. Correlation of the T/sub 4/ value between radioimmunoassay and CPBA in 69 patients was good (r=0.88612, p<0.01) and showed a slightly higher T/sub 4/ value when measured with radioimmunoassay than CPBA (linear regression function: Y=1.17506 + 0.95766X). Correlation of T/sub 4/ between Compu-curve and conventional standard curve was excellent (r=0.9995), but a slight difference was found in both low and high T/sub 4/ concentrations. In euthyroid patients without thyroid diseases, T/sub 4/ concentration was 9.92 +- 2.66 (SD) ..mu..g% and the normal range was between 4.60 and 15.24 ..mu..g%. Reproducibility within assay was 9.9% (CV) and recovery rate was 70% when added 10 ..mu..g of T/sub 4/ and 86% when added 15 ..mu..g% of T/sub 4/. From these results, the authors concluded that radioimmunoassay of serum T/sub 4/ using the T/sub 4/ RIA kit would be a promising one, especially when measuring a large amount of samples per assays.

  3. CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

    Science.gov (United States)

    Do, Jeong-Su; Visperas, Anabelle; O'Brien, Rebecca L; Min, Booki

    2012-04-01

    A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells. Here, we report that γδ T cells generated within αβ T cell (or CD4 T cell)-deficient environments displayed altered cytokine profiles; particularly, 'innate' IL-17 expression was significantly impaired compared with those in wild-type mice. Impaired IL-17 production in γδ T cells was directly related to CD4 T-cell deficiency, because depletion of CD4 T cells in wild-type mice diminished and adoptive CD4 T-cell transfer into T-cell receptor β-/- mice restored IL-17 expression in γδ T cells. CD4 T cell-mediated IL-17 expression required TGFβ1. Moreover, Th17 but not Th1 or Th2 effector CD4 T cells were highly efficient in enhancing γδ T-cell IL-17 expression. Taken together, our results highlight a novel CD4 T cell-dependent mechanism that shapes the generation of IL-17+ γδ T cells in naive settings.

  4. Human rotavirus specific T cells: quantification by ELISPOT and expression of homing receptors on CD4+ T cells

    International Nuclear Information System (INIS)

    Rojas, Olga Lucia; Gonzalez, Ana Maria; Gonzalez, Rosabel; Perez-Schael, Irene; Greenberg, Harry B.; Franco, Manuel A.; Angel, Juana

    2003-01-01

    Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4 + and CD8 + T cells secreting INFγ, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFγ-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4 + and CD8 + T cell subsets, IFNγ-secreting RV-specific CD8 + but not CD4 + T cells were detected in recently infected children. Using the same approach, both CD4 + and CD8 + RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte homing receptors demonstrated that RV-specific INFγ-secreting CD4 + T cells from adult volunteers preferentially express the intestinal homing receptor α4β7, but not the peripheral lymph node homing receptor L-selectin. In contrast, CMV-specific INFγ-secreting CD4 + T cells preferentially express L-selectin but not α4β7. These results suggest that the expression of homing receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFγ is independent of the expression of these homing receptors

  5. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.

    Science.gov (United States)

    Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L

    2017-09-15

    Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. The hand: MR imaging with a 4.7-T magnet

    International Nuclear Information System (INIS)

    Wang, P.C.; Archer, A.; Rajan, S.; Carvlin, M.J.; Mun, S.K.; Nelson, M.C.

    1987-01-01

    MR images of normal and pathologic human hands were obtained using a 4.7-T magnet Varian system. Standard spin-echo techniques and inversion-recovery sequences were used to produce both T1- and T2-weighted images. The higher gradient (2 gauss/cm) of the 4.7-T system allows submillimeter resolution. A specially designed surface coil is used to improve the signal-to-noise ratio. The coil is elliptical and measures 3 inches by 4.5 inches. Axial, coronal, and sagittal images were obtained, revealing fine, detailed structures of the human hand. The joint capsule, ligaments and tendons, and vascular structures were clearly visible. The authors will show images of the normal anatomy of the hand, as well as pathologic lesions of inflammatory and crystalline arthropathy. Techniques and special problems of imaging the human hand with a 4.7-T system are discussed

  7. Role of T-bet, the master regulator of Th1 cells, in the cytotoxicity of murine CD4+ T cells.

    Science.gov (United States)

    Eshima, Koji; Misawa, Kana; Ohashi, Chihiro; Iwabuchi, Kazuya

    2018-05-01

    Although CD4 + T cells are generally regarded as helper T cells, some activated CD4 + T cells have cytotoxic properties. Given that CD4 + cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4 + T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to expression of IFN-γ has been well-documented, it remains unclear whether T-bet is involved in CD4 + T cell-mediated cytotoxicity. In this study, to investigate the ability of T-bet to confer cytolytic activity on CD4 + T cells, the T-bet gene (Tbx21) was introduced into non-cytocidal CD4 + T cell lines and their cytolytic function analyzed. Up-regulation of FasL (CD178), which provided the transfectant with cytotoxicity, was observed in Tbx21transfected CD4 + T cells but not in untransfected parental cells. In one cell line, T-bet transduction also induced perforin gene (Prf1) expression and Tbx21 transfectants efficiently killed Fas - target cells. Although T-bet was found to repress up-regulation of CD40L (CD154), which controls FasL-mediated cytolysis, the extent of CD40L up-regulation on in vitro-differentiated Th1 cells was similar to that on Th2 cells, suggesting the existence of a compensatory mechanism. These results collectively indicate that T-bet may be involved in the expression of genes, such as FasL and Prf1, which confer cytotoxicity on Th1 cells. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  8. Different Competitive Capacities of Stat4 and Stat6 Deficient CD4+ T Cells during Lymphophenia-Driven Proliferation

    DEFF Research Database (Denmark)

    Sanchez-Guajardo, Vanesa Maria; Borghans, J.A.M.; Marquez, M.-E.

    2005-01-01

    The outcome of an immune response relies on the competitive capacities acquired through differentiation of CD4T cells into Th1 or Th2 effector cells. Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this study the kinetics...... of Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4T cells during competitive bone marrow reconstitution and lymphopenia-driven proliferation. After bone marrow transplantation, both populations reconstitute the peripheral T cell pools equally well. After transfer into lymphopenic hosts, wild-type and Stat6ﰐ/ﰐ CD4T cells...... show a proliferation advantage, which is early associated with the expression of an active phospho-Stat4 and the down-regulation of Stat6. Despite these differences, Stat4- and Stat6-deficient T cells reach similar steady state numbers. However, when both Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4T cells...

  9. Performance Evaluation of the MyT4 Technology for Determining ART Eligibility.

    Science.gov (United States)

    Sitoe, Nádia; Macamo, Rosa; Meggi, Bindiya; Tobaiwa, Ocean; Loquiha, Osvaldo; Bollinger, Timothy; Vojnov, Lara; Jani, Ilesh

    2016-01-01

    In resource-limited countries, CD4 T-cell (CD4) testing continues to be used for determining antiretroviral therapy (ART) initiation eligibility and opportunistic infection monitoring. To support expanded access to CD4 testing, simple and robust technologies are necessary. We conducted this study to evaluate the performance of a new Point-of-Care (POC) CD4 technology, the MyT4, compared to conventional laboratory CD4 testing. EDTA venous blood from 200 HIV-positive patients was tested in the laboratory using the MyT4 and BD FACSCalibur™. The MyT4 had an r2 of 0.82 and a mean bias of 12.3 cells/μl. The MyT4 had total misclassifications of 14.7% and 8.8% when analyzed using ART eligibility thresholds of 350 and 500 cells/μl, respectively. We conclude that the MyT4 performed well in classifying patients using the current ART initiation eligibility thresholds in Mozambique when compared to the conventional CD4 technology.

  10. Activity-based in vitro selection of T4 DNA ligase

    International Nuclear Information System (INIS)

    Takahashi, Fumio; Funabashi, Hisakage; Mie, Masayasu; Endo, Yaeta; Sawasaki, Tatsuya; Aizawa, Masuo; Kobatake, Eiry

    2005-01-01

    Recent in vitro methodologies for selection and directed evolution of proteins have concentrated not only on proteins with affinity such as single-chain antibody but also on enzymes. We developed a display technology for selection of T4 DNA ligase on ribosome because an in vitro selection method for DNA ligase had never been developed. The 3' end of mRNA encoding the gene of active or inactive T4 DNA ligase-spacer peptide fusion protein was hybridized to dsDNA fragments with cohesive ends, the substrate of T4 DNA ligase. After in vitro translation of the mRNA-dsDNA complex in a rabbit reticulocyte system, a mRNA-dsDNA-ribosome-ligase complex was produced. T4 DNA ligase enzyme displayed on a ribosome, through addition of a spacer peptide, is able to react with dsDNA in the complex. The complex expressing active ligase was biotinylated by ligation with another biotinylated dsDNA probe and selected with streptavidin-coated magnetic beads. We effectively selected active T4 DNA ligase from a small amount of protein. The gene of the active T4 DNA ligase was enriched 40 times from a mixture of active and inactive genes using this selection strategy. This ribosomal display strategy may have high potential to be useful for selection of other enzymes associated with DNA

  11. Experiments on the Making(T32 work in progress)

    DEFF Research Database (Denmark)

    Carbone, Claudia

    2016-01-01

    . This mode of operation entails production of derivative variations accommodating a reading of differences in the material as well as in the space in between, facilitating possibilities of chance encounters, discoveries. The work is developed as a fragmented assemblage of representations of T32 (acronym......, facilitator) of memories of the places of obliteration it exposes; the erasure of significance of the past, and possesses their validity in the present and the future. Methodological approaches explored in the contextual, the serial, relating to T32 its heterogeneous representations; the findings...

  12. Experiments on the Making(T32 work in progress)

    DEFF Research Database (Denmark)

    Carbone, Claudia

    2017-01-01

    of operation entails production of derivative variations accommodating a reading of differences in the material as well as in the space in between, facilitating possibilities of chance encounters, discoveries. The work is developed as a fragmented assemblage of representations of T32 (acronym – a road, 32......) of memories of the places of obliteration it exposes; the erasure of significance of the past, and possesses their validity in the present and the future.Methodological approaches explored in the contextual, the serial, relating to T32 its heterogeneous representations; the findings, the manipulated drawings...

  13. Demonstration of strong enterobacterial reactivity of CD4+CD25- T cells from conventional and germ-free mice which is counter-regulated by CD4+CD25+ T cells

    DEFF Research Database (Denmark)

    Gad, Monika; Pedersen, Anders Elm; Kristensen, Nanna N

    2004-01-01

    Unfractionated CD4+ T cells from the gut-associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro. Under similar conditions, CD4+ T cells depleted in vivo or in vitro of CD4+CD25+ T cells proliferate extensively. The CD4+CD25- T...

  14. An activating mutation of interferon regulatory factor 4 (IRF4) in adult T cell leukemia.

    Science.gov (United States)

    Cherian, Mathew A; Olson, Sydney; Sundaramoorthi, Hemalatha; Cates, Kitra; Cheng, Xiaogang; Harding, John; Martens, Andrew; Challen, Grant A; Tyagi, Manoj; Ratner, Lee; Rauch, Daniel

    2018-03-14

    The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL. Here high throughput whole-exome sequencing revealed recurrent activating genetic alterations in the T cell receptor, CD28, and NF-kB pathways. Moreover, we found that IRF4, which is transcriptionally activated downstream of these pathways, is frequently mutated in ATL. IRF4 RNA, protein, and IRF4 transcriptional targets are uniformly elevated in HTLV transformed cells and ATL cell lines, and IRF4 was bound to genomic regulatory DNA of many of these transcriptional targets in HTLV-1 transformed cell lines. We further noted that the K59R IRF4 mutant is expressed at higher levels in the nucleus than is wild-type IRF4, and is transcriptionally more active. Expression of both wild-type and the K59R mutant of IRF4 from a constitutive promoter in retrovirally transduced murine bone marrow cells increased the abundance of T lymphocytes but not myeloid cells or B lymphocytes in mice. IRF4 may represent a therapeutic target in ATL since ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and over-expression of IRF4 induces the expansion of T lymphocytes in vivo. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Treating Osteoarthritis of the Knee Popular: Supplements Don't Work

    Science.gov (United States)

    ... and Notes Stories Patients’ Stories Providers’ Stories Treating Osteoarthritis of the Knee Popular supplements don’t work osteoarthritis of the knee Lose excess weight . Losing a pound of excess ...

  16. The Transcription Factor Hobit Identifies Human Cytotoxic CD4(+) T Cells

    NARCIS (Netherlands)

    Oja, Anna E.; Vieira Braga, Felipe A.; Remmerswaal, Ester B. M.; Kragten, Natasja A. M.; Hertoghs, Kirsten M. L.; Zuo, Jianmin; Moss, Paul A.; van Lier, René A. W.; van Gisbergen, Klaas P. J. M.; Hombrink, Pleun

    2017-01-01

    The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that

  17. Experimental electromagnetic effects on the model organism Escherichia coli and the bacteriophage T4

    Science.gov (United States)

    Lisiewski, Darlene Mildred

    This experimentally-based work was designed to answer the research question as to whether the phenomenon of nuclear magnetic resonance (NMR) can produce observable effects upon the bacterial virus activity of T4, with such activity demonstrated through the infection of its host bacterium Escherichia coli. The biological samples were placed for three hours within a coil antenna assembly propagating oscillating fields of radio frequency electromagnetic energy generated at the frequency of 5.6 MHz, and set at right angles within a magnetic field of 1450 gauss (recognizing such conditions are not set for the maximum effective resonance for hydrogen nuclei). The laboratory technique of plaque formation was the basis upon which the statistically tested data were compiled. Exposure of the bacterium alone exhibited an increase in viral activity over the control group (40--68% higher numbers of plaque formation), while exposure of T4 alone saw a decrease (approximately 23%) in infection rates. Depending on the protocol, placement of both T4 and E. coli into the coil assembly saw a decrease of either approximately 50% or 42% in infection rates. Future research must address identification of the effects being observed.

  18. Critical role of γ4 chain in the expression of functional Vγ4Vδ1 T cell receptor of gastric tumour-infiltrating γδT lymphocytes.

    Science.gov (United States)

    Jiang, Y; Tang, F; Li, Z; Cui, L; He, W

    2012-01-01

    4Vδ1 T cell receptor (TCRγ4δ1)-expressing γδT cells were the most dominant subset in gastric tumour-infiltrating γδT cells (γδTIL) we recently analyzed. To study the essential roles of γ and δ chains in assembly and function of TCRγ4δ1, we sequenced and constructed them into lentiviral vectors for the reconstitution of TCRγ4δ1 using different modalities of transduction. We were able to efficiently reconstitute TCRγ4δ1 with functional activities when both γ4 and δ1 chains are coexpressed in TCR-negative J.RT3-T3.5 cells. However, the expression of δ1 chain is greatly diminished when γ4 expression is absent, suggesting that the coexpressing γ4 is critical in maintaining the folding and stability of δ1 product. To functionally study the reconstituted TCRγ4δ1, we examined the cytolytic activity of TCRγ4δ1-reconstituted J.RT3-T3.5 cells and cytokine secretion and found the receptors are fully functional, but their functionality also requires the presence of γ4. Our results demonstrated that γ4 is critical for the stability of δ1 and the function of TCRγ4δ1. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  19. Early universe cosmology and tests of fundamental physics

    International Nuclear Information System (INIS)

    Albrecht, Andreas; Frieman, Joshua A.; Trodden, Mark

    2002-01-01

    This is the report of the Working Group on Early Universe Cosmology and tests of Fundamental Physics, group P4.8 of the of the Snowmass 2001 conference. Here we summarize the impressive array of advances that have taken place in this field, and identify opportunities for even greater progress in the future. Topics include Dark Energy, Cosmic Acceleration, Inflation, Phase Transitions, Baryogenesis, and String/M-theory Cosmology. The introductory section gives an executive summary with six key open questions on which we can expect to make significant progress

  20. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  1. α4β7+ CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection.

    Science.gov (United States)

    Cheung, Ka-Wai; Wu, Tongjin; Ho, Sai Fan; Wong, Yik Chun; Liu, Li; Wang, Hui; Chen, Zhiwei

    2018-04-15

    HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α 4 β 7 + gut-homing CCR7 - CD4 + effector/effector memory T cells (T EM ) and results in massive depletion of these cells and other subsets of T EM in gut-associated lymphoid tissues. However, besides being eliminated by HIV-1, the role of T EM during the early stage of infection remains inconclusive. Here, using in vitro -induced α 4 β 7 + gut-homing T EM (α 4 β 7 + T EM ), we found that α 4 β 7 + T EM differentiated into CCR7 + CD4 + central memory T cells (T CM ). This differentiation was HIV-1 independent but was inhibited by SB431542, a specific transforming growth factor β (TGF-β) receptor I kinase inhibitor. Consistently, T EM -to-T CM differentiation was observed in α 4 β 7 + T EM stimulated with TGF-β1 (TGF-β). The T CM properties of the TGF-β-induced T EM -derived T CM (α 4 β 7 + T CM ) were confirmed by their enhanced CCL19 chemotaxis and the downregulation of surface CCR7 upon T cell activation in vitro Importantly, the effect of TGF-β on T CM differentiation also held in T EM directly isolated from peripheral blood. To investigate the significance of the TGF-β-dependent T EM -to-T CM differentiation in HIV/AIDS pathogenesis, we observed that both productively and latently infected α 4 β 7 + T CM could differentiate from α 4 β 7 + T EM in the presence of TGF-β during HIV-1 infection. Collectively, this study not only provides a new insight for the plasticity of T EM but also suggests that the TGF-β-dependent T EM -to-T CM differentiation is a previously unrecognized mechanism for the formation of latently infected T CM after HIV-1 infection. IMPORTANCE HIV-1 is the causative agent of HIV/AIDS, which has led to millions of deaths in the past 30 years. Although the implementation of highly active antiretroviral therapy has remarkably reduced the HIV-1-related morbidity and mortality, HIV-1 is not eradicated in

  2. CD4 T-Cell Memory Generation and Maintenance

    Science.gov (United States)

    Gasper, David J.; Tejera, Melba Marie; Suresh, M.

    2014-01-01

    Immunologic memory is the adaptive immune system's powerful ability to remember a previous antigen encounter and react with accelerated vigor upon antigen re-exposure. It provides durable protection against reinfection with pathogens and is the foundation for vaccine-induced immunity. Unlike the relatively restricted immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell memory must account for multiple distinct lineages with diverse effector functions, the issue of lineage commitment and plasticity, and the variable distribution of memory cells within each lineage. Here, we discuss the evidence for lineage-specific CD4 T-cell memory and summarize the known factors contributing to memory-cell generation, plasticity, and long-term maintenance. PMID:24940912

  3. CD4+ Foxp3+ T-cells contribute to myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Mathes, Denise; Weirather, Johannes; Nordbeck, Peter; Arias-Loza, Anahi-Paula; Burkard, Matthias; Pachel, Christina; Kerkau, Thomas; Beyersdorf, Niklas; Frantz, Stefan; Hofmann, Ulrich

    2016-12-01

    The present study analyzed the effect of CD4 + Forkhead box protein 3 negative (Foxp3 - ) T-cells and Foxp3 + CD4 + T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4 + T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34.5±4.7% in MHCII KO versus 59.4±4.9% in wildtype (WT)) and better preserved ejection fraction determined by magnetic resonance tomography (56.9±2.8% in MHC II KO versus 39.0±4.2% in WT). MHC-II KO mice also displayed better microvascular perfusion than WT mice after 24hours of reperfusion. Also CD4 + T-cell sufficient OT-II mice, which express an in this context irrelevant T-cell receptor, revealed smaller infarct sizes compared to WT mice. However, MHC-II blocking anti-I-A/I-E antibody treatment was not able to reduce infarct size indicating that autoantigen recognition is not required for the activation of CD4 + T-cells during reperfusion. Flow-cytometric analysis also did not detect CD4 + T-cell activation in heart draining lymph nodes in response to 24hours of ischemia-reperfusion. Adoptive transfer of CD4 + T-cells in CD4 KO mice increased the infarct size only when including the Foxp3 + CD25 + subset. Depletion of CD4 + Foxp3 + T-cells in DEREG mice enabling specific conditional ablation of this subset by treatment with diphtheria toxin attenuated infarct size as compared to diphtheria toxin treated WT mice. CD4 + Foxp3 + T-cells enhance myocardial ischemia-reperfusion injury. CD4 + T-cells exert injurious effects without the need for prior activation by MHC-II restricted autoantigen recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. ImmunoPET Imaging of Murine CD4+ T Cells Using Anti-CD4 Cys-Diabody: Effects of Protein Dose on T Cell Function and Imaging.

    Science.gov (United States)

    Freise, Amanda C; Zettlitz, Kirstin A; Salazar, Felix B; Lu, Xiang; Tavaré, Richard; Wu, Anna M

    2017-08-01

    Molecular imaging of CD4 + T cells throughout the body has implications for monitoring autoimmune disease and immunotherapy of cancer. Given the key role of these cells in regulating immunity, it is important to develop a biologically inert probe. GK1.5 cys-diabody (cDb), a previously developed anti-mouse CD4 antibody fragment, was tested at different doses to assess its effects on positron emission tomography (PET) imaging and CD4 + T cell viability, proliferation, CD4 expression, and function. The effect of protein dose on image contrast (lymphoid tissue-to-muscle ratio) was assessed by administering different amounts of 89 Zr-labeled GK1.5 cDb to mice followed by PET imaging and ex vivo biodistribution analysis. To assess impact of GK1.5 cDb on T cell biology, GK1.5 cDb was incubated with T cells in vitro or administered intravenously to C57BL/6 mice at multiple protein doses. CD4 expression and T cell proliferation were analyzed with flow cytometry and cytokines were assayed. For immunoPET imaging, the lowest protein dose of 2 μg of 89 Zr-labeled GK1.5 cDb resulted in significantly higher % injected dose/g in inguinal lymph nodes (ILN) and spleen compared to the 12-μg protein dose. In vivo administration of GK1.5 cDb at the high dose of 40 μg caused a transient decrease in CD4 expression in spleen, blood, lymph nodes, and thymus, which recovered within 3 days postinjection; this effect was reduced, although not abrogated, when 2 μg was administered. Proliferation was inhibited in vivo in ILN but not the spleen by injection of 40 μg GK1.5 cDb. Concentrations of GK1.5 cDb in excess of 25 nM significantly inhibited CD4 + T cell proliferation and interferon-γ production in vitro. Overall, using low-dose GK1.5 cDb minimized biological effects on CD4 + T cells. Low-dose GK1.5 cDb yields high-contrast immunoPET images with minimal effects on T cell biology in vitro and in vivo and may be a useful tool for investigating CD4 + T cells in the context of

  5. Efecto de la raza y la edad sobre las concentraciones de hormonas tiroideas T3 y T4 de bovinos en condiciones tropicales Effect of the breed and age on the thyroid hormones T3 and T4 concentrations in bovines under tropical conditions

    Directory of Open Access Journals (Sweden)

    Rómulo Campos Gaona

    2008-06-01

    Full Text Available Para estudiar el efecto en condiciones de trópico seco de la edad y del grupo racial sobre las concentraciones séricas de las hormonas tiroideas T3 y T4, se muestrearon 158 animales de los grupos raciales Holstein, Lucerna, Hartón del Valle, Cebú Brahman y mestizo F1 (Cebú Brahman x Pardo Suizo, distribuidos en cuatro grupos de edad desde el nacimiento hasta el destete (8 meses. La concentración media de T3 fue 2.25 mmol/L y la de T4, 57.37 mmol/L. La correlación entre T3 y T4 fue de 0.53. Se encontró diferencia estadísticamente significativa para el efecto grupo racial, grupo de edad (PTo study the effect of age and breed on blood concentration of thyroid hormones T3 and T4 under the dry tropic conditions, 158 animals from the groups Holstein, Lucerna, Hartón del Valle, Brahman and crossbred F1 Brahman x Brown Swiss were sampled. The animals were allocated in four age groups from newborns calves until eight month old. The average T3 concentration was of 2.25 mmolL-¹ and the T4 was of 57.37 mmolL-¹. The correlation between T3 and T4 was of 0.53. A statistical significant difference (p<0.001 was found for the effects of age breed and group, but not difference was found for the interaction between breed and age (p=0.286. The breeds with higher blood concentrations of T3 and T4 were Holstein and Lucerna. The lowest concentration was found among the crossbred group. The higher concentration of T3 and T4 of thyroid hormones was found in the newborn group. As the calves grow, the concentrations of T3 and T4 decrease progressively. This study found that under dry tropic conditions, in a thermo-neutral borderline zone (according to the THI index the young bovines show clear differences in the concentration of the thyroid hormones

  6. Flow-cytometric measurement of CD4-8- T cells bearing T-cell receptor αβ chains, 1

    International Nuclear Information System (INIS)

    Kusunoki, Yoichiro; Hirai, Yuko; Kyoizumi, Seishi; Akiyama, Mitoshi.

    1992-09-01

    In this study we detected rare, possibly abnormal, T cells bearing CD3 surface antigen and T-cell receptor (TCR) αβ chains but lacking both CD4 and CD8 antigens (viz., TCRαβ + CD4 - 8 - cells, as determined by flow cytometry). The TCRαβ + CD4 - 8 - T cells were detected at a mean frequency of 0.63 ± 0.35 % (mean ± standard deviation) in peripheral blood TCRαβ + cells of 119 normal persons. Two unusual cases besides the 119 normal persons showed extremely elevated frequencies of TCRαβ + CD4 - 8 - T cells, viz., approximately 5 % to 10 % and 14 % to 19 % in whole TCRαβ + cells. Both individuals were males who were otherwise physiologically quite normal with no history of severe illness, and these high frequencies were also observed in blood samples collected 2 or 8 years prior to the current measurements. The TCRαβ + CD4 - 8 - T cells of the two individuals were found to express mature T-cell markers such as CD2,3, and 5 antigens, as well as natural killer (NK) cell markers, viz., CD11b, 16, 56, and 57 antigens, when peripheral blood lymphocytes were subjected to three-color flow cytometry. Lectin-dependent or redirected antibody-dependent cell-mediated cytotoxicities were observed for both freshly sorted TCRαβ + CD4 - 8 - cells and in vitro established clones. Nevertheless, NK-like activity was not detected. Further, Southern blot analysis of TCRβ and γ genes revealed identical rearrangement patterns for all the TCRαβ + CD4 - 8 - clones established in vitro. These results suggest that the TCRαβ + CD4 - 8 - T cells from these two mean exhibit unique characteristics and proliferate clonally in vivo. (author)

  7. The T -786C, G894T, and Intron 4 VNTR (4a/b) Polymorphisms of the Endothelial Nitric Oxide Synthase Gene in Prostate Cancer Cases.

    Science.gov (United States)

    Diler, S B; Öden, A

    2016-02-01

    In previously conducted some studies it has been revealed that nitric oxide (NO) and nitric oxide synthase (NOS) system play a significant role in carcinogenesis. Nitric oxide (NO) is regulated by endothelial nitric oxide synthase (eNOS) enzyme which is one of the isoenzymes of NO synthase (NOS). In this study we have tried to come to a conclusion about whether eNOS gene T -786C, G894T and Intron 4 VNTR (4a/b) polymorphisms might be considered as a risk factor causing prostate cancer (PCa) or not. A total of 200 subjects were included in this research. 84 patients with PCa (mean age 70.0 ± 6.4) and 116 healthy controls (mean age 69.9 ± 7.5) were recruited in this case-control study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Maryland, USA), according to the manufacturer's guidelines. The T-786C, G894T and Intron 4 VNTR (4a/b) polymorphisms were amplified using polymerase chain reation (PCR), detected by restriction fragment length polymorphism (RFLP). For T -786C polymorphism CC genotype [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.15-0.78, P = 0.009)] and allele frequency (OR: 0.631, CI: 0.421-0.946, P = 0.026) is significant for control. In patients with PCa eNOS G894T polymorphism, both GT (OR: 0.069, CI: 0.027-0.174; P = 0.0001) and TT (OR: 0.040, CI: 0.013-0.123; P = = 0.0001) genotype distribution, and also T allele frequency (OR: 0.237, CI: 0.155-0.362, P = 0.0001) were considered significant statistically. While genotype distribution for the other polymorphism eNOS, intron 4 VNTR (4a/b), is insignificant statistically, "a" allele frequency was found out to be significant (OR: 2.223, CI: 1.311-3.769, P = 0.003). In this study we indicated that genotype and allele frequencies of eNOS T -786C and G894T polymorphisms are statistically significant in patients with PCa. eNOS T -786C and G894T polymorphisms may be associated with PCa susceptibility in the Turkish population. In contrast, intron 4 VNTR (4a

  8. MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Yicheng Qi

    2017-11-01

    Full Text Available ContextAberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD. MicroRNAs (miRNAs are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear.ObjectiveTo investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.MethodsWe compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated.ResultsGD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40, while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression.ConclusionThe increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.

  9. Bacteriophage T4 Nanoparticles as Materials in Sensor Applications: Variables That Influence Their Organization and Assembly on Surfaces

    Directory of Open Access Journals (Sweden)

    Jinny L. Liu

    2009-08-01

    Full Text Available Bacteriophage T4 nanoparticles possess characteristics that make them ideal candidates as materials for sensors, particularly as sensor probes. Their surface can be modified, either through genetic engineering or direct chemical conjugation to display functional moieties such as antibodies or other proteins to recognize a specific target. However, in order for T4 nanoparticles to be utilized as a sensor probe, it is necessary to understand and control the variables that determine their assembly and organization on a surface. The aim of this work is to discuss some of variables that we have identified as influencing the behavior of T4 nanoparticles on surfaces. The effect of pH, ionic strength, substrate characteristics, nanoparticle concentration and charge was addressed qualitatively using atomic force microscopy (AFM.

  10. Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes.

    Science.gov (United States)

    Westhorpe, Clare L V; Norman, M Ursula; Hall, Pam; Snelgrove, Sarah L; Finsterbusch, Michaela; Li, Anqi; Lo, Camden; Tan, Zhe Hao; Li, Songhui; Nilsson, Susan K; Kitching, A Richard; Hickey, Michael J

    2018-02-21

    Although effector CD4 + T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4 + T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4 + T cells. Following intravascular deposition of antigen in glomeruli, effector CD4 + T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII + immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4 + T-cell-dependent glomerular inflammation. These findings indicate that MHCII + monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4 + T cells within glomerular capillaries, leading to antigen-dependent inflammation.

  11. Role of 4-1BB receptor in the control played by CD8(+ T cells on IFN-gamma production by Mycobacterium tuberculosis antigen-specific CD4(+ T Cells.

    Directory of Open Access Journals (Sweden)

    Carla Palma

    Full Text Available BACKGROUND: Antigen-specific IFN-gamma producing CD4(+ T cells are the main mediators of protection against Mycobacterium tuberculosis infection both under natural conditions and following vaccination. However these cells are responsible for lung damage and poor vaccine efficacy when not tightly controlled. Discovering new tools to control nonprotective antigen-specific IFN-gamma production without affecting protective IFN-gamma is a challenge in tuberculosis research. METHODS AND FINDINGS: Immunization with DNA encoding Ag85B, a candidate vaccine antigen of Mycobacterium tuberculosis, elicited in mice a low but protective CD4(+ T cell-mediated IFN-gamma response, while in mice primed with DNA and boosted with Ag85B protein a massive increase in IFN-gamma response was associated with loss of protection. Both protective and non-protective Ag85B-immunization generated antigen-specific CD8(+ T cells which suppressed IFN-gamma-secreting CD4(+ T cells. However, ex vivo ligation of 4-1BB, a member of TNF-receptor super-family, reduced the massive, non-protective IFN-gamma responses by CD4(+ T cells in protein-boosted mice without affecting the low protective IFN-gamma-secretion in mice immunized with DNA. This selective inhibition was due to the induction of 4-1BB exclusively on CD8(+ T cells of DNA-primed and protein-boosted mice following Ag85B protein stimulation. The 4-1BB-mediated IFN-gamma inhibition did not require soluble IL-10, TGF-beta, XCL-1 and MIP-1beta. In vivo Ag85B stimulation induced 4-1BB expression on CD8(+ T cells and in vivo 4-1BB ligation reduced the activation, IFN-gamma production and expansion of Ag85B-specific CD4(+ T cells of DNA-primed and protein-boosted mice. CONCLUSION/SIGNIFICANCE: Antigen-specific suppressor CD8(+ T cells are elicited through immunization with the mycobacterial antigen Ag85B. Ligation of 4-1BB receptor further enhanced their suppressive activity on IFN-gamma-secreting CD4(+ T cells. The selective

  12. Gut-homing CD4+ T cell receptor alpha beta+ T cells in the pathogenesis of murine inflammatory bowel disease

    DEFF Research Database (Denmark)

    Rudolphi, A; Boll, G; Poulsen, S S

    1994-01-01

    reconstituted a CD3+ T cell receptor alpha beta+ CD4+ T cell subset. CD4+ cells of this subset expressed the surface phenotype of mucosa-seeking, memory T cells. In the immunodeficient scid host, this gut-derived CD4+ T cell subset was found in spleen, peritoneal cavity, mesenteric lymph nodes (LN), epithelial...... compartments with CD4+ T cells from normal GALT plays an essential role in the pathogenesis of IBD in an immunodeficient host.......We studied which T cell subsets from the gut-associated lymphoid tissue (GALT) can migrate out of the gut mucosa and repopulate GALT compartments of an immunodeficient (semi)syngeneic host. Many distinct lymphocyte subsets were found in GALT of immunocompetent H-2d (BALB/c, BALB/cdm2, C.B-17...

  13. IFNγ-producing CD4+ T lymphocytes: the double-edged swords in tuberculosis.

    Science.gov (United States)

    Kumar, Pawan

    2017-12-01

    IFNγ-producing CD4 + T cells (IFNγ + CD4 + T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ + CD4 + T cells in TB pathogenesis. High frequency of IFNγ + CD4 + T cells is the most invariable feature of the active disease. Active TB patients mount a heightened IFNγ + CD4 + T cell response to mycobacterial antigens and demonstrate an IFNγ-inducible transcriptomic signature. IFNγ + CD4 + T cells have also been shown to mediate TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) observed in a subset of antiretroviral therapy (ART)-treated HIV- and Mtb-coinfected people. The pathological face of IFNγ + CD4 + T cells during mycobacterial infection is further uncovered by studies in the animal model of TB-IRIS and in Mtb-infected PD-1 -/- mice. This manuscript encompasses the evidence supporting the dual role of IFNγ + CD4 + T cells during Mtb infection and sheds light on immune mechanisms involved in protection versus pathogenesis.

  14. Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease.

    Science.gov (United States)

    Mattoo, Hamid; Stone, John H; Pillai, Shiv

    2017-02-01

    IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4 + T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated. Among the CD4 + T-cell subsets, Th2 cells were initially thought to contribute to IgG4-RD pathogenesis, but many previous studies were confounded by the concomitant history of allergic diseases in the patients studied and the failure to use multi-color staining to definitively identify T-cell subsets in tissue samples. More recently, using an unbiased approach to characterize CD4 + T-cell subsets in patients with IgG4-RD - based on their clonal expansion and ability to infiltrate affected tissue sites - CD4 + CTLs have been identified as the major CD4 + T-cell subset in disease lesions as well as in the circulation. CD4 + CTLs in affected tissues secrete pro-fibrotic cytokines including IL-1β, TGF-β1, and IFN-γ as well as cytolytic molecules such as perforin and granzymes A and B. In this review, we examine possible mechanisms by which activated B cells and plasmablasts may collaborate with the expanded CD4 + CTLs in driving the fibrotic pathology of the disease and describe the lacunae in the field and in our understanding of IgG4-RD pathogenesis.

  15. SYNTHESIS OF TETRA-p-PROPENYLTETRAESTERCALIX[4]ARENE AND TETRA-p-PROPENYLTETRACARBOXYLICACIDCALIX[4]ARENE FROM p-t-BUTYLPHENOL

    Directory of Open Access Journals (Sweden)

    Triana Kusumaningsih

    2010-06-01

    Full Text Available A research has been conducted to synthesize tetra-p-propenyltetraestercalix[4]arene and tetra-p-propenyltetracarboxylicacidcalix[4] arene using p-t-butylphenol as a starting material. The synthesis was carried out in following stages, i.e (1 synthesis of p-t-butylcalix[4]arene from p-t-butylphenol, (2 debutylation of p-t-butylcalix[4]arene, (3 tetraallilation of 25,26,27,28-tetrahydroxycalix[4]arene with NaH and allilbromida in dry tetrahydrofuran, (4 Claissen rearrangement of 25,26,27,28-tetrapropenyloxycalix[4]arene, (5 esterification of tetra-p-propenyltetrahydroxycalix[4]arene, (6 hydrolisis of tetra-p-propenyltetraestercalix[4]arene. The all structures of products were observed by means of melting point, FTIR, and 1H-NMR spectrometers. Tetra-p-propenyltetraestercalix[4]arene compound was obtained as yellow liquid product in 55.08% yield. Tetra-p-propenyltetracarboxylicacidcalix[4]arene compound was obtained as white solid product with the melting point 135-137 °C at decomposed and in 70.05% yield.   Keywords: calix[4]arene, Claissen rearrangement, esterification, hydrolisis

  16. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2007-05-01

    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  17. Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.

    Science.gov (United States)

    Orlova-Fink, Nina; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-10-23

    The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.

  18. Characterization of CD4+ T cell-mediated cytotoxicity in patients with multiple myeloma.

    Science.gov (United States)

    Zhang, Xiaole; Gao, Lei; Meng, Kai; Han, Chunting; Li, Qiang; Feng, Zhenjun; Chen, Lei

    2018-05-01

    Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls. The frequencies of cytotoxic CD4 T cells in MM patients were not associated with the frequencies of cytotoxic CD8 T cells, but were negatively associated with disease severity. Interestingly, the expression levels of inhibitory molecules, including PD-1 and CTLA-4, were significantly lower in cytotoxic CD4 T cells than in cytotoxic CD8 T cells. When co-incubated with autologous CD38 + CD138 + plasma cells, CD4 T cells were capable of eliminating plasma cells with varying degrees of efficacy. In MM patients, the frequency of circulating plasma cells was negatively correlated with the frequency of cytotoxic CD4 T cells. Therefore, CD4 T cell-mediated cytotoxicity existed naturally in MM patients and could potentially act as an option in antitumor therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C, on Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Anahí Magdaleno

    Full Text Available It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C. The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC(50 = 0.89+/-0.02 mM at 28 degrees C, and the inhibitory effect of this analogue was synergistic (p<0.05 with temperature (0.54+/-0.01 mM at 37 degrees C. T4C significantly diminished parasite survival (p<0.05 in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM. All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.

  20. Substitution of 125-I-T3, 125-I-T4 and 125-I-TSH produced in the ININ, in commercial boxes for radioimmunoessay

    International Nuclear Information System (INIS)

    Delgado S, B.; Zambrano A, F.; Lavalley E, C.; Ferro F, G.; Lezama C, J.

    1991-03-01

    Due to the half, relatively short life, of the I-125 used in the radioinmunoanalisis (he/she LAUGHS) of hormones realcionadas with the thyroid, frequently it is observed that they are the other reagents of commercial cases without using, reason for the one which you piede the possibility to use in their entirety statements kits for the CREEK, what causes lost economic and another type of deficiencies. Presently work the results are presented obtained on the characteristics of quality of commercial stuches for the CREEK of hormones of the thyroid profile (T3, T4 and TSH), after substituting to the different radiotrazadores in this cases. The marcaje of the hormones with I-125 was made by means of the method of the cloramina T with 25 seconds of reaction for each hormone, purifying the T3 and the T4 for cromatografia liquidates of high efficiency and to the TSH for cromatografia of likeness in a column of cellulose microcristalina of 6 x 0.8 cm. the substitution of the radiotrazador is made in the commercial cases and the protocol was continued proposed by the makers, giving a coefficient of correlation of -0-997, as a result after the comparison of the straight line among the cases without and with substitution of the radiotrazador; besides certain parameters of quality of the such rehearsals as: the maximum unions (50%+-5) and inespecifica (<5%), slope of the straight line (-2.1 + - 0.2), and other coming from the use of samples of control of quality. We can conclude that at the moment we have in the ININ radiotrazadores of T3, T4 and TSH of good quality, like to be substituted in commercial cases and to use this way to the maximum these games of reagents that are so expensive. (Author)

  1. Blood Pressure Medicines Don’t Work If People Don’t Take Them PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2016-09-13

    This 60 second public service announcement is based on the September 2016 CDC Vital Signs report. Blood pressure medicines don’t work if people don’t take them. Learn how health care systems can work with patients to make taking medicines easier.  Created: 9/13/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/13/2016.

  2. Facile Synthesis of Highly Water-Soluble Lanthanide-Doped t-LaVO4 NPs for Antifake Ink and Latent Fingermark Detection

    KAUST Repository

    Chen, Cailing

    2017-11-08

    In the information age, it is important to protect the security and integrity of the information. As a result, the fluorescent ink as an antifake technology and the fingermark as an information carrier have aroused great interest. In this work, highly water-soluble lanthanide (Ln3+ )-doped tetragonal phase (t-) LaVO4 nanoparticles (NPs) are successfully obtained via a simple, fast, and green microwave-assisted hydrothermal method. The average size of t-LaVO4 NPs is about 43 nm. The aqueous solutions of Ln3+ -doped t-LaVO4 exhibit excellent fluorescence properties under ultraviolet light (UV) excitation (t-LaVO4 :10%Eu is bright red and t-LaVO4 :0.5%Dy is close to white). Some superb antifake fluorescent patterns are printed using Ln3+ -doped t-LaVO4 aqueous solution as ink, which indicates the as-prepared Ln3+ -doped t-LaVO4 NPs as fluorescent ink can meet the various antifake requirements. Notably, the designed convenient antifake fluorescent codes with improved security could be directly scanned and decoded by a smart phone. What\\'s more, the as-prepared NPs can be used for the development of latent fingermark on various substrates and the second-level detail information can be clearly obtained from the magnification of a fingermark. These results indicate that the as-prepared Ln3+ -doped t-LaVO4 fluorescent NPs have great potential in security application.

  3. Facile Synthesis of Highly Water-Soluble Lanthanide-Doped t-LaVO4 NPs for Antifake Ink and Latent Fingermark Detection

    KAUST Repository

    Chen, Cailing; Yu, Ying; Li, Chunguang; Liu, Dan; Huang, He; Liang, Chen; Lou, Yue; Han, Yu; Shi, Zhan; Feng, Shouhua

    2017-01-01

    In the information age, it is important to protect the security and integrity of the information. As a result, the fluorescent ink as an antifake technology and the fingermark as an information carrier have aroused great interest. In this work, highly water-soluble lanthanide (Ln3+ )-doped tetragonal phase (t-) LaVO4 nanoparticles (NPs) are successfully obtained via a simple, fast, and green microwave-assisted hydrothermal method. The average size of t-LaVO4 NPs is about 43 nm. The aqueous solutions of Ln3+ -doped t-LaVO4 exhibit excellent fluorescence properties under ultraviolet light (UV) excitation (t-LaVO4 :10%Eu is bright red and t-LaVO4 :0.5%Dy is close to white). Some superb antifake fluorescent patterns are printed using Ln3+ -doped t-LaVO4 aqueous solution as ink, which indicates the as-prepared Ln3+ -doped t-LaVO4 NPs as fluorescent ink can meet the various antifake requirements. Notably, the designed convenient antifake fluorescent codes with improved security could be directly scanned and decoded by a smart phone. What's more, the as-prepared NPs can be used for the development of latent fingermark on various substrates and the second-level detail information can be clearly obtained from the magnification of a fingermark. These results indicate that the as-prepared Ln3+ -doped t-LaVO4 fluorescent NPs have great potential in security application.

  4. Association between ε2/3/4, Promoter Polymorphism (−491A/T, −427T/C, and −219T/G at the Apolipoprotein E Gene, and Mental Retardation in Children from an Iodine Deficiency Area, China

    Directory of Open Access Journals (Sweden)

    Jun Li

    2014-01-01

    Full Text Available Background. Several common single-nucleotide polymorphisms (SNPs at apolipoprotein E (ApoE have been linked with late onset sporadic Alzheimer’s disease and declining normative cognitive ability in elder people, but we are unclear about their relationship with cognition in children. Results. We studied -491A/T, -427T/C, and -219G/T promoter polymorphisms and ε2/ε3/ε4 at ApoE among children with mental retardation (MR, n=130, borderline MR (n=124, and controls (n=334 from an iodine deficiency area in China. The allelic and genotypic distribution of individual locus did not significantly differ among three groups with Mantel-Haenszel χ2 test (P>0.05. However, frequencies of haplotype of -491A/-427T/-219T4 were distributed as MR > borderline MR > controls (P uncorrected = 0.004, indicating that the presence of this haplotype may increase the risk of disease. Conclusions. In this large population-based study in children, we did not find any significant association between single locus of the four common ApoE polymorphisms (-491A/T, -427T/C, -219T/G, and ε2/3/4 and MR or borderline MR. However, we found that the presence of ATTε4 haplotype was associated with an increased risk of MR and borderline MR. Our present work may help enlarge our knowledge of the cognitive role of ApoE across the lifespan and the mechanisms of human cognition.

  5. [Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats].

    Science.gov (United States)

    Wei, Ming; Tu, Ling; Liang, Yinghong; Li, Jia; Gong, Yanjie; Zhang, Yihua; Yang, Lu

    2015-09-01

    To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats. Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all Pcells and macrophages (r=0.5126, 0.5437, all Pcells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.

  6. No significant effect of prefrontal tDCS on working memory performance in older adults

    Directory of Open Access Journals (Sweden)

    Jonna eNilsson

    2015-12-01

    Full Text Available Transcranial direct current stimulation (tDCS has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1mA and 2mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

  7. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    Science.gov (United States)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-02-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

  8. Survival of T4aN0 and T3N+ laryngeal cancer patients: a retrospective institutional study and systematic review.

    Science.gov (United States)

    Khoueir, Nadim; Matar, Nayla; Farah, Chadi; Francis, Evana; Tabchy, Bassam; Haddad, Amine

    2015-01-01

    We aim to assess the correlation of tumor and nodal staging to survival in pT3N+ and T4aN0 laryngeal cancer with subgroup analysis within stage IVa (pT4N0 and pT3N2). Retrospective cohort study with systematic review of the literature. Hotel Dieu de France University Hospital (tertiary referral center). Laryngeal cancer patients' registries were reviewed from 1998 to 2012 selecting pT3N+ and pT4aN0 patients treated by primary total layngectomy. Overall survivals were compared using Log rank and Kaplan-Meier analysis. A systematic review was performed by 2 reviewers including all the articles reporting the outcome of these categories of patients. Online databases, including PubMed and EMBASE, were used. Reference sections of identified studies were examined for additional articles. Thirteen T3N+ patients and 19 T4aN0 patients treated by primary total laryngectomy were included. Five-year overall survival for T3N+, T3N2 and T4aN0 was respectively 33%, 32.1% and 73.7%. Due to the small sample, the difference was not significant. The systematic review revealed three articles reporting overall survival outcome for the T4N0 group and 6 articles for the T3N+. At 5years, the survival ranged from 62.5% to 73% in T4N0 and from 32.2% to 77% in T3N+. In advanced stage laryngeal cancer, T4aN0 tends toward a better survival than T3N+ especially when compared to T3N2 although they are grouped in the same TNM stage IVa. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Determination of serum free thyroxine concentration (FT4) by means of fT4-fraction and total thyroxine concentration

    International Nuclear Information System (INIS)

    Passath, A.; Leb, G.

    1985-01-01

    A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT 4 -fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT 4 ) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT 4 fraction readings. The 'euthyroid reference range' of FT 4 (SPAC ET) was between 0.70 to 1.78ng/dl. This euthyroid range of FT 4 was determined from TT 4 concentrations measured by T 4 -RIA (SPAC T 4 MONO) which were 30% above TT 4 values measured by conventional T 4 -RIA (SPAC T 4 POLY; polyclonal antibodies). However, a different euthyroid range of FT 4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T 4 -RIA measurements were used for calculation of FT 4 values. Our results indicate that calculated FT 4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducability of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended. (Author)

  10. The CD4+CD26-T-cell population in classical Hodgkin's lymphoma displays a distinctive regulatory T-cell profile

    NARCIS (Netherlands)

    Ma, Yue; Visser, Lydia; Blokzijl, Tjasso; Harms, Geert; Atayar, Cigdem; Poppema, Sibrand; van den Berg, Anke

    Little is known about the gene expression profile and significance of the rosetting CD4+CD26- T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4+CD26- and CD4+CD26+ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL)

  11. Summary of the snowmass working group on machine-detector interface

    International Nuclear Information System (INIS)

    Bharadwaj, V.; Colestock, P.; Cooper, J.; Goderre, G.; Holt, J.

    1993-01-01

    From the detector point of view, what experimenters need is an outline of the EXPECTED machine parameters tempered with some indication of the POSSIBLE machine parameters. Given guidance from accelerator physicists on the machine, experimenters may get the germ of an idea of how to exploit a particular machine property. Similarly, given some indication of what is important to the experimenters, accelerator physicists may have ideas of how to modify the machine appropriately. The authors discuss a list of machine parameters from the perspective of experimentalists. These include: luminosity; number of bunches/bunch spacing; beam energy; luminosity lifetime; β * /longitudinal emittance; transverse emittance. They also include a summary of tevatron performance - past, present, and projected

  12. Regulatory function of cytomegalovirus-specific CD4+CD27-CD28- T cells

    International Nuclear Information System (INIS)

    Tovar-Salazar, Adriana; Patterson-Bartlett, Julie; Jesser, Renee; Weinberg, Adriana

    2010-01-01

    CMV infection is characterized by high of frequencies of CD27 - CD28 - T cells. Here we demonstrate that CMV-specific CD4 + CD27 - CD28 - cells are regulatory T cells (T R ). CD4 + CD27 - CD28 - cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4 + T-cell population, higher proportions of CD4 + CD27 - CD28 - T R expressed FoxP3, TGFβ, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4 + CD27 - CD28 - T R expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4 + CD27 - CD28 - T R significantly decreased after granzyme B or TGFβ inhibition. The CMV-CD4 + CD27 - CD28 - T R of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4 + CD27 - CD28 - T R . The CMV-CD4 + CD27 - CD28 - T R may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.

  13. Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells.

    Science.gov (United States)

    Elgueta, Raul; Sepulveda, Fernando E; Vilches, Felipe; Vargas, Leonardo; Mora, J Rodrigo; Bono, Maria Rosa; Rosemblatt, Mario

    2008-05-15

    It has recently been shown that IL-4 can educate dendritic cells (DC) to differentially affect T cell effector activity. In this study, we show that IL-4 can also act upon DC to instruct naive T cells to express the gut-associated homing receptor CCR9. Thus, effector T cells generated after coculture with mesenteric lymph node (MLN)-DC show a higher expression of CCR9 when activated in the presence of IL-4. In contrast, IL-4 had no effect on CCR9 expression when naive T cells were polyclonally activated in the absence of MLN-DC, suggesting that the effect of IL-4 on CCR9 expression passed through DC. Indeed, T cells activated by MLN-DC from IL-4Ralpha(-/-) mice showed a much lower CCR9 expression and a greatly reduced migration to the small intestine than T cells activated by wild-type MLN-DC even in the presence of IL-4. Consistent with the finding that the vitamin A metabolite retinoic acid (RA) induces gut-homing molecules on T cells, we further demonstrate that IL-4 up-regulated retinaldehyde dehydrogenase 2 mRNA on MLN-DC, a critical enzyme involved in the synthesis of RA. Moreover, LE135, a RA receptor antagonist, blocked the increased expression of CCR9 driven by IL-4-treated MLN-DC. Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC.

  14. Significance of lymphadenectomy with splenectomy in radical surgery for advanced (pT3/pT4) remnant gastric cancer.

    Science.gov (United States)

    Sugita, Hiroki; Oda, Eri; Hirota, Masahiko; Ishikawa, Shinji; Tomiyasu, Shinjiro; Tanaka, Hiroshi; Arita, Tetsumasa; Yagi, Yasushi; Baba, Hideo

    2016-04-01

    To date, the optimal surgical strategy for remnant gastric cancer has not been determined. The purpose of this study was to clarify the significance of lymphadenectomy with splenectomy in remnant gastric cancer surgery. This retrospective cohort study was conducted at the Kumamoto Regional Medical Center. The primary endpoint was overall survival after surgery. We retrospectively analyzed the clinicopathologic features, surgical treatments, and long-term prognosis of remnant gastric cancer patients treated with total gastrectomy. A total of 80 patients with gastric cancer in the remnant stomach after distal gastrectomy and who underwent total gastrectomy were enrolled in the study. Splenectomy was performed in 38 patients. Lymph node metastasis in the splenic hilum was not observed in the patients with pT1/pT2 tumors, whereas nodal metastasis at the splenic hilum was detected in 30.4% of the patients with pT3/pT4 tumors. The survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy, although there was no difference in the patients with pT1/pT2 tumors. Among the patients classified as R0, the survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy. Lymphadenectomy with splenectomy in radical surgery is beneficial for patients with advanced (pT3/pT4) remnant gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  16. Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

    Science.gov (United States)

    Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

    2013-11-01

    It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P 350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

  17. Role of LAP+CD4+ T cells in the tumor microenvironment of colorectal cancer.

    Science.gov (United States)

    Zhong, Wu; Jiang, Zhi-Yuan; Zhang, Lei; Huang, Jia-Hao; Wang, Shi-Jun; Liao, Cun; Cai, Bin; Chen, Li-Sheng; Zhang, Sen; Guo, Yun; Cao, Yun-Fei; Gao, Feng

    2017-01-21

    To investigate the abundance and potential functions of LAP + CD4 + T cells in colorectal cancer (CRC). Proportions of LAP + CD4 + T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box (Fox)p3, cytotoxic T-lymphocyte-associated protein (CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP - CD4 + and LAP + CD4 + T cells were isolated using a magnetic cell-sorting system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. The proportion of LAP + CD4 + T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P CD4 + T cells was significantly higher in tumor tissues (11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P CD4 + T cells and TNM stage ( P cell sorting gave an overall enrichment of LAP + CD4 + T cells (95.02% ± 2.87%), which was similar for LAP - CD4 + T cells (94.75% ± 2.76%). In contrast to LAP - CD4 + T cells, LAP + CD4 + T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and CCR5 ( P CD4 + T cells expressed significantly larger amounts of IL-10 and TGF-β but lower levels of IL-2, IL-4, IL-17 and interferon-γ, compared with LAP - CD4 + T cells. LAP + CD4 + T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-β.

  18. CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization

    NARCIS (Netherlands)

    Xiao, Yanling; Peperzak, Victor; Keller, Anna M.; Borst, Jannie

    2008-01-01

    For optimal quality, memory CD8(+) T cells require CD4(+) T cell help. We have examined whether CD4(+) T cells require CD27 to deliver this help, in a model of intranasal OVA protein immunization. CD27 deficiency reduced the capacity of CD4(+) T cells to support Ag-specific CD8(+) T cell

  19. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  20. n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation.

    Science.gov (United States)

    Hou, Tim Y; Monk, Jennifer M; Fan, Yang-Yi; Barhoumi, Rola; Chen, Yong Q; Rivera, Gonzalo M; McMurray, David N; Chapkin, Robert S

    2012-04-01

    n-3 PUFA (polyunsaturated fatty acids), i.e. DHA (docosahexaenoic acid), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since PtdIns(4,5)P2 resides in raft domains and DHA can alter the size of rafts, we hypothesized that PtdIns(4,5)P2 and downstream actin remodelling are perturbed by the incorporation of n-3 PUFA into membranes, resulting in suppressed T-cell activation. CD4+ T-cells isolated from Fat-1 transgenic mice (membranes enriched in n-3 PUFA) exhibited a 50% decrease in PtdIns(4,5)P2. Upon activation by plate-bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T-cells failed to metabolize PtdIns(4,5)P2. Furthermore, actin remodelling failed to initiate in Fat-1 CD4+ T-cells upon stimulation; however, the defect was reversed by incubation with exogenous PtdIns(4,5)P2. When Fat-1 CD4+ T-cells were stimulated with anti-CD3/anti-CD28-coated beads, WASP (Wiskott-Aldrich syndrome protein) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PtdIns(4,5)P2 metabolism and actin remodelling, were recapitulated in CD4+ T-cells isolated from mice fed on a 4% DHA triacylglycerol-enriched diet. Collectively, these data demonstrate that n-3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells.

  1. Advances in hybrid MR–PET at 3 T and 9.4 T in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jon Shah, N., E-mail: n.j.shah@fz-juelich.de [Institute of Neuroscience and Medicine-4, Research Centre Jülich, 52425 Jülich (Germany); Department of Neurology, Faculty of Medicine, JARA, RWTH Aachen University Aachen (Germany); Mauler, Jörg [Institute of Neuroscience and Medicine-4, Research Centre Jülich, 52425 Jülich (Germany); Neuner, Irene [Institute of Neuroscience and Medicine-4, Research Centre Jülich, 52425 Jülich (Germany); Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen (Germany); Oros-Peusquens, Ana-Maria; Romanzetti, Sandro; Vahedipour, Kaveh; Felder, Jörg; Celik, Avdo [Institute of Neuroscience and Medicine-4, Research Centre Jülich, 52425 Jülich (Germany); Iida, Hidehiro [Department of Investigative Radiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, 565-8565 (Japan); Langen, Karl-Josef; Herzog, Hans [Institute of Neuroscience and Medicine-4, Research Centre Jülich, 52425 Jülich (Germany)

    2013-02-21

    Hybrid MR–PET data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are demonstrated. Examples of tumour imaging on a 3 T MR–PET system are included and discussed.

  2. Advances in hybrid MR–PET at 3 T and 9.4 T in humans

    International Nuclear Information System (INIS)

    Jon Shah, N.; Mauler, Jörg; Neuner, Irene; Oros-Peusquens, Ana-Maria; Romanzetti, Sandro; Vahedipour, Kaveh; Felder, Jörg; Celik, Avdo; Iida, Hidehiro; Langen, Karl-Josef; Herzog, Hans

    2013-01-01

    Hybrid MR–PET data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are demonstrated. Examples of tumour imaging on a 3 T MR–PET system are included and discussed

  3. CD4~+Foxp3~+ regulatory T cells converted by rapamycin from peripheral CD4~+ CD25~-naive T cells display more potent regulatory ability in vitro

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-fei; GAO Jie; ZHANG Dong; WANG Zi-han; ZHU Ji-ye

    2010-01-01

    Background Rapamycin (RAPA) is a relatively new immunosuppressant drug that functions as a serine/threonine kinase inhibitor to prevent rejection in organ transplantation. RAPA blocks activation of T-effector (Teff) cells by inhibiting the response to interleukin-2. Recently, RAPA was also shown to selectively expand the T-regulator (Treg) cell population. To date, no studies have examined the mechanism by which RAPA converts Teff cells to Treg cells. Methods Peripheral CD4~+CD25~- naive T cells were cultivated with RAPA and B cells as antigen-presenting cells (APCs) in vitro. CD4~+CD25~- T cells were harvested after 6 days and analyzed for expression of forkhead box protein 3 (Foxp3) using flow cytometry. CD4~+CD25~+CD127~- subsets as the converted Tregs were isolated from the mixed lymphocyte reactions (MLR) with CD127 negative selection, followed by CD4 and CD25 positive selection using microbeads and magnetic separation column (MSC). Moreover, mRNA was extracted from converted Tregs and C57BL/6 naive CD4~+CD25~+ T cells and Foxp3 levels were examined by quantitative real-time polymerase chain reaction (rt-PCR). A total of 1×10~5 carboxyfluorescein succinimidyl ester (CFSE)-labeled naive CD4~+CD25~- T cells/well from C57BL/6 mice were cocultured with DBA/2 or C3H maturation of dendritic cells (mDCs) (0.25×10~5/well) in 96-well round-bottom plates for 6 days. Then 1×10~5 or 0.25×10~5 converted Treg cells were added to every well as regulatory cells. Cells were harvested after 6 days of culture and analyzed for proliferation of CFSE-labeled naive CD4~+CD25~- T cells using flow cytometry. Data were analyzed using CellQuest software.Results We found that RAPA can convert peripheral CD4~+CD25~- naive T Cells to CD4~+Foxp3~+ Treg cells using B cells as APCs, and this subtype of Treg can potently suppress Teff proliferation and maintain antigenic specificity. Conclusion Our findings provide evidence that RAPA induces Treg cell conversion from Teff cells and

  4. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    NARCIS (Netherlands)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-01-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is

  5. The early history of tRNA recognition by aminoacyl-tRNA synthetases

    Indian Academy of Sciences (India)

    Madhu

    2006-10-04

    Oct 4, 2006 ... Discovery of aminoacyl-tRNA synthetases and importance ... The pioneering work of Fritz Lipmann on the high-energy ... the peculiar structural and functional relationships tRNAs ... a bulk of only 20 families of tRNA molecules in contrast ...... balance of tRNA and aminoacyl-tRNA synthetase; Science 242.

  6. Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2012-01-01

    in general or myelin-reactive T-cells in particular showed signs of increased immune activation. Furthermore we examined the effects of natalizumab on CD4(+) T-cell responses to myelin in vitro. Natalizumab-treated MS patients had significantly increased numbers of effector-memory T-cells in the blood. In T-cells......(HIGH) T-cells, in blood, and natalizumab decreased the expression of CD134 on MBP-reactive CD26(HIGH)CD4(+) T-cells in vitro. Otherwise CD4(+) T-cells from natalizumab-treated and untreated MS patients showed similar responses to MBP. In conclusion natalizumab treatment selectively increased...... transmigration of circulating immune-cells across the vascular endothelium into the CNS. Recent studies suggested that natalizumab treated MS patients have an increased T-cell pool in the blood compartment which may be selectively enriched in activated T-cells. Proposed causes are sequestration of activated T-cells...

  7. Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

    Directory of Open Access Journals (Sweden)

    Arundhoti Das

    Full Text Available Naïve CD4 T (NCD4T cells post-activation undergo programming for inducible production of cytokines leading to generation of memory cells with various functions. Based on cytokine based polarization of NCD4T cells in vitro, programming for either 'Th1' (interferon-gamma [IFNg] or 'Th2' (interleukin [IL]-4/5/13 cytokines is thought to occur via mutually exclusive expression and functioning of T-bet or GATA-3 transcription factors (TFs. However, we show that a high proportion of mouse and human memory-phenotype CD4 T (MCD4T cells generated in vivo which expressed either Th1 or Th2 cytokines commonly co-expressed T-bet and GATA-3. While T-bet levels did not differ between IFNg-expressing and IL-4/5/13-expressing MCD4T cells, GATA-3 levels were higher in the latter. These observations were also confirmed in MCD4T cells from FVB/NJ or aged C57BL/6 or IFNg-deficient mice. While MCD4T cells from these strains showed greater Th2 commitment than those from young C57BL/6 mice, pattern of co-expression of TF was similar. Effector T cells generated in vivo following immunization also showed TF co-expression in Th1 or Th2 cytokine producing cells. We speculated that the difference in TF expression pattern of MCD4T cells generated in vivo and those generated in cytokine polarized cultures in vitro could be due to relative absence of polarizing conditions during activation in vivo. We tested this by NCD4T cell activation in non-polarizing conditions in vitro. Anti-CD3 and anti-CD28-mediated priming of polyclonal NCD4T cells in vitro without polarizing milieu generated cells that expressed either IFNg or IL-4/5/13 but not both, yet both IFNg- and IL-4/5/13-expressing cells showed upregulation of both TFs. We also tested monoclonal T cell populations activated in non-polarizing conditions. TCR-transgenic NCD4T cells primed in vitro by cognate peptide in non-polarizing conditions which expressed either IFNg or IL-4/5/13 also showed a high proportion of cells co

  8. A novel SIV gag-specific CD4(+)T-cell clone suppresses SIVmac239 replication in CD4(+)T cells revealing the interplay between antiviral effector cells and their infected targets.

    Science.gov (United States)

    Ayala, Victor I; Trivett, Matthew T; Coren, Lori V; Jain, Sumiti; Bohn, Patrick S; Wiseman, Roger W; O'Connor, David H; Ohlen, Claes; Ott, David E

    2016-06-01

    To study CD4(+)T-cell suppression of AIDS virus replication, we isolated nine rhesus macaque SIVGag-specific CD4(+)T-cell clones. One responding clone, Gag68, produced a typical cytotoxic CD8(+)T-cell response: induction of intracellular IFN-γ, MIP-1α, MIP-1β, and CD107a degranulation. Gag68 effectively suppressed the spread of SIVmac239 in CD4(+)T cells with a corresponding reduction of infected Gag68 effector cells, suggesting that CD4(+)effectors need to suppress their own infection in addition to their targets to be effective. Gag68 TCR cloning and gene transfer into CD4(+)T cells enabled additional experiments with this unique specificity after the original clone senesced. Our data supports the idea that CD4(+)T cells can directly limit AIDS virus spread in T cells. Furthermore, Gag68 TCR transfer into CD4(+)T-cell clones with differing properties holds promise to better understand the suppressive effector mechanisms used by this important component of the antiviral response using the rhesus macaque model. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Circadian variations of thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4) in surgical and functional pinealectomy in rats

    International Nuclear Information System (INIS)

    Ostrowska, Z.; Zwirska-Korczala, K.; Buntner, B.; Jarzab, B.; Kucharzewski, M.

    1994-01-01

    The aim of the present study was to determine the regulatory influence of surgical and functional pinealectomy on circadian variations of thyrotropin (TSH), triiodothyronine (T 3 ) and thyroxine (T 4 ) in male Wistar rats. The serum hormone levels were estimated with RIA method, and the circadian rhythm secretion was analyzed by means of cosinor method. Our study shows that there are marked differences in circadian fluctuations of T 3 and T 4 between the two generally used models of pinealectomy. (author). 55 refs, 4 figs

  10. Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus.

    OpenAIRE

    Takahashi, K; Sonoda, S; Higashi, K; Kondo, T; Takahashi, H; Takahashi, M; Yamanishi, K

    1989-01-01

    Human herpesvirus 6 (HHV-6)-related virus was isolated from CD4+ CD8- and CD3+ CD4+ mature T lymphocytes but could not be isolated from CD4- CD8+, CD4- CD8-, and CD3- T cells in the peripheral blood of exanthem subitum patients. HHV-6-related virus predominantly infected CD4+ CD8+, CD4+ CD8-, and CD3+ CD4+ cells with mature phenotypes and rarely infected CD4- CD8+ cells from cord blood mononuclear cells, which suggested predominant CD4 mature T-lymphocyte tropism of HHV-6-related virus.

  11. Quantitation of T-3 (triiodothyronine) and T-4 (thyroxine) in serum and plasma. Draft report

    International Nuclear Information System (INIS)

    Ceglowski, W.; Williams, R.B.

    1981-12-01

    This report summarizes an examination of the published literature concerning the quantitation of thyroxine and triiodothyronine in the clinical laboratory. It therefore details the precision, accuracy, sensitivity, and specificity obtainable in various commercial systems and those devised in the clinical laboratory. The data produced by several of the procedures often indicate that improvements in these parameters would enhance overall assay performance and increase the reliability of the clinical interpretation derivable from assay results. For T-3 and T-4 in vitro assays a very large number of systems exist and are currently being utilized in clinical laboratories in this country. For the sake of brevity some systems, while mentioned, are not reviewed in exhaustive detail. Radioimmunoassay, as the most frequently performed assay for both T-3 and T-4 is extensively reviewed. Also discussed with particular interest are assay systems which will undoubtedly impact on the future course of thyroid hormone assessment in the clinical laboratory, namely enzyme immunoassay and fluorescent immunoassay. The state of the art in T-4 measurements in neonates, because it is such a critical area for application of in vitro thyroid testing, is given detailed review. The quantitation of free thyroxine has been discussed in detail. These assays have been gaining more frequent use in the clinical laboratory and increased commercial system development

  12. In situ depletion of CD4(+) T cells in human skin by Zanolimumab

    DEFF Research Database (Denmark)

    Villadsen, L.S.; Skov, L.; Dam, T.N.

    2007-01-01

    CD4(+) T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease......-driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4(+) T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, kappa) against CD4, was studied in a human psoriasis......(+), but not CD8(+) CD3(+) T cells. The capacity of Zanolimumab to deplete the CD4(+) T cells in the skin may be of importance in diseases where CD4(+) T cells play a central role. Indeed, in a phase II clinical trial Zanolimumab has shown a dose-dependent clinical response in patients with CTCL and the antibody...

  13. Functional Heterogeneity in the CD4+ T Cell Response to Murine γ-Herpesvirus 68

    Science.gov (United States)

    Hu, Zhuting; Blackman, Marcia A.; Kaye, Kenneth M.; Usherwood, Edward J.

    2015-01-01

    CD4+ T cells are critical for the control of virus infections, T cell memory and immune surveillance. Here we studied the differentiation and function of murine γ-herpesvirus 68 (MHV-68)-specific CD4+ T cells using gp150-specific TCR transgenic mice. This allowed a more detailed study of the characteristics of the CD4+ T cell response than previously available approaches for this virus. Most gp150-specific CD4+ T cells expressed T-bet and produced IFN-γ, indicating MHV-68 infection triggered differentiation of CD4+ T cells largely into the Th1 subset, whereas some became TFH and Foxp3+ regulatory T cells. These CD4+ T cells were protective against MHV-68 infection, in the absence of CD8+ T cells and B cells, and protection depended on IFN-γ secretion. Marked heterogeneity was observed in the CD4+ T cells, based on Ly6C expression. Ly6C expression positively correlated with IFN-γ, TNF-α and granzyme B production, T-bet and KLRG1 expression, proliferation and CD4+ T cell-mediated cytotoxicity. Ly6C expression inversely correlated with survival, CCR7 expression and secondary expansion potential. Ly6C+ and Ly6C− gp150-specific CD4+ T cells were able to interconvert in a bidirectional manner upon secondary antigen exposure in vivo. These results indicate that Ly6C expression is closely associated with antiviral activity in effector CD4+ T cells, but inversely correlated with memory potential. Interconversion between Ly6C+ and Ly6C− cells may maintain a balance between the two antigen-specific CD4+ T cell populations during MHV-68 infection. These findings have significant implications for Ly6C as a surface marker to distinguish functionally distinct CD4+ T cells during persistent virus infection. PMID:25662997

  14. HIV-1 induces DCIR expression in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Alexandra A Lambert

    2010-11-01

    Full Text Available The C-type lectin receptor DCIR, which has been shown very recently to act as an attachment factor for HIV-1 in dendritic cells, is expressed predominantly on antigen-presenting cells. However, this concept was recently challenged by the discovery that DCIR can also be detected in CD4(+ T cells found in the synovial tissue from rheumatoid arthritis (RA patients. Given that RA and HIV-1 infections share common features such as a chronic inflammatory condition and polyclonal immune hyperactivation status, we hypothesized that HIV-1 could promote DCIR expression in CD4(+ T cells. We report here that HIV-1 drives DCIR expression in human primary CD4(+ T cells isolated from patients (from both aviremic/treated and viremic/treatment naive persons and cells acutely infected in vitro (seen in both virus-infected and uninfected cells. Soluble factors produced by virus-infected cells are responsible for the noticed DCIR up-regulation on uninfected cells. Infection studies with Vpr- or Nef-deleted viruses revealed that these two viral genes are not contributing to the mechanism of DCIR induction that is seen following acute infection of CD4(+ T cells with HIV-1. Moreover, we report that DCIR is linked to caspase-dependent (induced by a mitochondria-mediated generation of free radicals and -independent intrinsic apoptotic pathways (involving the death effector AIF. Finally, we demonstrate that the higher surface expression of DCIR in CD4(+ T cells is accompanied by an enhancement of virus attachment/entry, replication and transfer. This study shows for the first time that HIV-1 induces DCIR membrane expression in CD4(+ T cells, a process that might promote virus dissemination throughout the infected organism.

  15. Activated CD4+T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation

    NARCIS (Netherlands)

    Banczyk, David; Kalies, Kathrin; Nachbar, Lars; Bergmann, Lars; Schmidt, Philipp; Bode, Ulrike; Teegen, Bianca; Steven, Philipp; Lange, Tanja; Textor, Johannes; Ludwig, Ralf J.; Stöcker, Winfried; König, Peter; Bell, Eric; Westermann, Jürgen

    2014-01-01

    CD4+T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+T cells may influence the function of

  16. Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T.

    Science.gov (United States)

    Hagberg, G E; Bause, J; Ethofer, T; Ehses, P; Dresler, T; Herbert, C; Pohmann, R; Shajan, G; Fallgatter, A; Pavlova, M A; Scheffler, K

    2017-01-01

    Mapping of the longitudinal relaxation time (T 1 ) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T 1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T 2 -dependent variation of the adiabatic inversion efficiency were investigated by single slice T 1 mapping with inversion recovery EPI measurements, quantitative T 2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T 1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T 1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T 1 estimates at high field, the proposed correction methods resulted in an improved precision, with test-retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. CD 4 + CD 25 + T cells maintain homeostasis by promoting TER - 119 cell development and inhibiting T cell activation

    Directory of Open Access Journals (Sweden)

    Muhaimin Rifa’i

    2014-05-01

    Full Text Available CD4+ CD25+ regulatory T cells involved in the regulation of self- tolerance and normality of homeostasis. CD122 deficient mice are model animals that have an abnormal immune system characteristically have a high number of activated T cells and TER-119 cell decreased. Here we showed evidence that the transfer of CD4+ CD25+ regulatory T cells derived from normal mice to CD122- defficient neonates prevent the development of activated memory T cells and elicit TER-119 differentiation. Bone marrow reconstitution derived from CD122-/- mice to normal mice resulting tolerance to individual that genetically different. Importantly, CD4+ CD25+ regulatory T cells derived from normal mice can replace CD4+ CD25+ cells derived from CD122-/- mice. The results of this experiment suggest that regulatory T cells from normal mice exert a critical role in maintaining peripheral tolerance and controlling hematopoietic disorder.

  18. Multiple dendritic cell populations activate CD4+ T cells after viral stimulation.

    Directory of Open Access Journals (Sweden)

    Adele M Mount

    2008-02-01

    Full Text Available Dendritic cells (DC are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8alpha DC play a prominent, and sometimes exclusive, role in driving amplification of CD8(+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4(+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4(+ and CD8(+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8alpha DC populations in the amplification of CD8(+ and CD4(+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8(+ T cells are dominated by presentation of antigen by CD8alpha DC but can involve non-CD8alpha DC. In contrast, CD4(+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4(+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity.

  19. Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases.

    Directory of Open Access Journals (Sweden)

    Craig B Wilen

    2011-04-01

    Full Text Available HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5 virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4 in place of or in addition to CCR5 (R5X4 remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals.

  20. Selective Expansion of Memory CD4+ T cells By Mitogenic Human CD28 Generates Inflammatory Cytokines and Regulatory T cells

    Science.gov (United States)

    Singh, Manisha; Basu, Sreemanti; Camell, Christina; Couturier, Jacob; Nudelman, Rodolfo J.; Medina, Miguel A.; Rodgers, John R.; Lewis, Dorothy E.

    2009-01-01

    Co-stimulatory signals are important for development of effector and regulatory T cells. In this case, CD28 signaling is usually considered inert in the absence of signaling through the TCR. By contrast, mitogenic rat CD28 mAbs reportedly expand regulatory T cells without TCR stimulation. We found that a commercially available human CD28 mAb (ANC28) stimulated PBMCs without TCR co-ligation or cross-linking; ANC28 selectively expanded CD4+CD25+FoxP3−(T effector) and CD4+CD25+FoxP3+ (Treg) cells. ANC28 stimulated the CD45RO+ CD4+ (memory) population whereas CD45RA+CD4+ (naïve) cells did not respond. ANC28 also induced inflammatory cytokines. Treg induced by ANC28 retain the Treg phenotype longer than did co-stimulated Treg. Treg induced by ANC28 suppressed CD25− T cells through a contact-dependent mechanism. Purity influenced the response of CD4+CD25+ cells because bead-purified CD4+CD25+ cells (85–90% pure) responded strongly to ANC28, whereas 98% pure FACS-sorted CD4+CD25 bright (T-reg) did not respond. Purified CD4+CD25int cells responded similarly to the bead-purified CD4+CD25+ cells. Thus, pre-activated CD4+ T cells (CD25int) respond to ANC28 rather than Treg (CD25bright). The ability of ANC28 to expand both effectors producing inflammatory cytokines as well as suppressive regulatory T cells might be useful for ex vivo expansion of therapeutic T cells. PMID:18446791

  1. Aluminum triiodide induced complexation and structural rearrangement of the hexaphospha-pentaprismane cage, P6C4tBu4

    International Nuclear Information System (INIS)

    Al-Ktaifani, M. M.

    2009-01-01

    Treatment of P 6 C 4 t Bu 4 with the Lewis acid AlI 3 in toluene at room temperature unexpectedly results in a structural rearrangement affording the ionic complex [P 6 C 4 t Bu 4 H][AlI 4 ] which was fully characterized by multinuclear NMR spectroscopy and a single crystal X-ray diffraction study. Supportive evidence that the reaction might involve a simple intermediate Lewis acid-base adduct [AlI 3 (η 1 -P 6 C 4 t Bu 4 )] came from the isolation on one occasion of small number of crystals of the bis-Al adduct [(AlI)μ-(P 6 C 4 t Bu 4 )(AlI 3 )], whose molecular structure was also confirmed by a single crystal X-ray diffraction study. (author)

  2. Coupling between magnetic, dielectric properties and crystal structure in MnT2O4 (T = V, Cr, Mn)

    International Nuclear Information System (INIS)

    Suzuki, T; Adachi, K; Katsufuji, T

    2006-01-01

    We measured the temperature dependence of dielectric constant and striction for spinel MnT 2 O 4 (T = V, Cr, Mn) under magnetic field. We found critical changes of the dielectric constant and striction with ferrimagnetic ordering as well as applied magnetic field in MnV 2 O 4 and Mn 3 O 4 , which have orbital degree of freedom in the T 3+ ion. This result indicates the importance of the orbital degree of freedom for the coupling between dielectric, magnetic properties and crystal structure in these spinel compounds

  3. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

    Science.gov (United States)

    Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

    2018-01-01

    The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

  4. Computational modeling of heterogeneity and function of CD4+ T cells

    Directory of Open Access Journals (Sweden)

    Adria eCarbo

    2014-07-01

    Full Text Available The immune system is composed of many different cell types and hundreds of intersecting molecular pathways and signals. This large biological complexity requires coordination between distinct pro-inflammatory and regulatory cell subsets to respond to infection while maintaining tissue homeostasis. CD4+ T cells play a central role in orchestrating immune responses and in maintaining a balance between pro- and anti- inflammatory responses. This tight balance between regulatory and effector reactions depends on the ability of CD4+ T cells to modulate distinct pathways within large molecular networks, since dysregulated CD4+ T cell responses may result in chronic inflammatory and autoimmune diseases. The CD4+ T cell differentiation process comprises an intricate interplay between cytokines, their receptors, adaptor molecules, signaling cascades and transcription factors that help delineate cell fate and function. Computational modeling can help to describe, simulate, analyze, and predict some of the behaviors in this complicated differentiation network. This review provides a comprehensive overview of existing computational immunology methods as well as novel strategies used to model immune responses with a particular focus on CD4+ T cell differentiation.

  5. Notch controls the survival of memory CD4+ T cells by regulating glucose uptake.

    Science.gov (United States)

    Maekawa, Yoichi; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Yagita, Hideo; Yasutomo, Koji

    2015-01-01

    CD4+ T cells differentiate into memory T cells that protect the host from subsequent infection. In contrast, autoreactive memory CD4+ T cells harm the body by persisting in the tissues. The underlying pathways controlling the maintenance of memory CD4+ T cells remain undefined. We show here that memory CD4+ T cell survival is impaired in the absence of the Notch signaling protein known as recombination signal binding protein for immunoglobulin κ J region (Rbpj). Treatment of mice with a Notch inhibitor reduced memory CD4+ T cell numbers and prevented the recurrent induction of experimental autoimmune encephalomyelitis. Rbpj-deficient CD4+ memory T cells exhibit reduced glucose uptake due to impaired AKT phosphorylation, resulting in low Glut1 expression. Treating mice with pyruvic acid, which bypasses glucose uptake and supplies the metabolite downstream of glucose uptake, inhibited the decrease of autoimmune memory CD4+ T cells in the absence of Notch signaling, suggesting memory CD4+ T cell survival relies on glucose metabolism. Together, these data define a central role for Notch signaling in maintaining memory CD4+ T cells through the regulation of glucose uptake.

  6. SIGNIFICANCE OF THYROID PROFILE (Serum T3, T4 & TSH IN INFERTILE WOMEN

    Directory of Open Access Journals (Sweden)

    Bindu Sharma

    2012-06-01

    Full Text Available Objective: To evaluate the relation of female infertility to thyroid dysfunction. Material & Methods: The present study was carried out in the department of Biochemistry in collaboration with the Gynae & Obst deptt., Subharti Medical College & Hospital Meerut. Serum T3, T4 and TSH estimation was done by Enzyme Linked Fluorescent Assay. Results: Serum T3 level in control group was 1.8 ± 0.64 nmol/L while it was 10.5 ± 0.5 nmol/L in hyperthyroid (p value 0.05, i.e., not significant. Serum TSH in control group was 3.5 ± 1.71 mIU/L, while it was 0.14 ± 0.01 mIU/L (p value <0.001, i.e., highly significant in hyperthyroidism, 8.4 ± 1.06 mIU/L in hypothyroidism (p value <0.001, i.e., highly significant. Out of 65 patients of study group thyroid dysfunction was associated with 25 (38.5% infertile women. 23 (35.4% women had hypothyroidism, 2 (3.1% women had hyperthyroidism and 40 women (61.5% were with euthyroid state, while in control group all the 25 women had euthyroid profile. Conclusions: Every infertile woman with ovulatory dysfunction should also investigated thyroid profile along with other investigations, to open better prospects of conception for such desperate infertile women.

  7. Human CD4 restores normal T cell development and function in mice deficient in murine CD4

    OpenAIRE

    1994-01-01

    The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

  8. Cytotoxic T lymphocyte associated molecule -4 (CTLA-4 gene polymorphisms in ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Sirous Naeimi

    2010-09-01

    Full Text Available Background: Ovarian cancer is a relatively common cancer among postmenopausal women. Nowadays, there is controversy about immunotherapy of ovarian cancer patients with interleukins such as interferon to reach better out come in prognosis of patients under chemotherapy. CTLA-4 is a gene, which has an important role in homeostasis and regulation of immune response. Inhibitory nature of CTLA-4 is proved to be of significance in autoimmune diseases as well as in cancer. In this study we intend to find out the relationship between polymorphisms of this gene at the sites of +49 A/G and -318 C/T and ovarian cancer.Methods: The polymorphisms of the CTLA-4 gene at the sites of +49 A/G exon and -318 C/T promoter were investigated. Blood samples of 73 patients with ovarian cancer and 115 healthy subjects used for DNA extraction. Two groups genotypes and alleles were determined using PCR method and compared by statistical t-student test.Results: There was no statistically significant difference in genotypes and alleles prevalence of +49 A/G and -317 C/T between two groups (p>0.05.Conclusion: Further researches with larger sample size while paying attention to the relation between the gene polymorphism and stage and type of tumor is recommended.

  9. IL-7 signaling imparts polyfunctionality and stemness potential to CD4+ T cells

    Science.gov (United States)

    Ding, Zhi-Chun; Liu, Chufeng; Cao, Yang; Habtetsion, Tsadik; Kuczma, Michal; Pi, Wenhu; Kong, Heng; Cacan, Ercan; Greer, Susanna F.; Cui, Yan; Blazar, Bruce R.; Munn, David H.; Zhou, Gang

    2016-01-01

    ABSTRACT The functional status of CD4+ T cells is a critical determinant of antitumor immunity. Polyfunctional CD4+ T cells possess the ability to concomitantly produce multiple Th1-type cytokines, exhibiting a functional attribute desirable for cancer immunotherapy. However, the mechanisms by which these cells are induced are neither defined nor it is clear if these cells can be used therapeutically to treat cancer. Here, we report that CD4+ T cells exposed to exogenous IL-7 during antigenic stimulation can acquire a polyfunctional phenotype, characterized by their ability to simultaneously express IFNγ, IL-2, TNFα and granzyme B. This IL-7-driven polyfunctional phenotype was associated with increased histone acetylation in the promoters of the effector genes, indicative of increased chromatin accessibility. Moreover, forced expression of a constitutively active (CA) form of STAT5 recapitulated IL-7 in inducing CD4+ T-cell polyfunctionality. Conversely, the expression of a dominant negative (DN) form of STAT5 abolished the ability of IL-7 to induce polyfunctional CD4+ T cells. These in-vitro-generated polyfunctional CD4+ T cells can traffic to tumor and expand intratumorally in response to immunization. Importantly, adoptive transfer of polyfunctional CD4+ T cells following lymphodepletive chemotherapy was able to eradicate large established tumors. This beneficial outcome was associated with the occurrence of antigen epitope spreading, activation of the endogenous CD8+ T cells and persistence of donor CD4+ T cells exhibiting memory stem cell attributes. These findings indicate that IL-7 signaling can impart polyfunctionality and stemness potential to CD4+ T cells, revealing a previously unknown property of IL-7 that can be exploited in adoptive T-cell immunotherapy. PMID:27471650

  10. Concentrações plasmáticas de testosterona, triiodotironina (T3 e tiroxina (T4 em bodes submetidos ao estresse calórico Plasma concentrations of testosterone, triiodothyronine (T3, and thyroxine (T4 in bucks submitted to heat stress

    Directory of Open Access Journals (Sweden)

    L.A. Coelho

    2008-12-01

    Full Text Available Para verificar o efeito do estresse calórico (EC nas concentrações plasmáticas de testosterona, triiodotironina (T3 e tiroxina (T4, oito bodes, das raças Saanen (n=4 e Alpina (n=4, foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC durante 30 dias e, após um período (60 dias de descanso, submetidos ao EC (23,7ºC a 34,0ºC por 30 dias. Para minimizar as variações sazonais nos perfis hormonais devido ao fotoperíodo, durante toda fase experimental, incluindo a de adaptação em condições de termoneutralidade (30 dias, o fotoperíodo foi controlado utilizando-se alternância de dias longos (16h de luz e 8h de escuro e de dias curtos (8h de luz e 16h de escuro a cada 30 dias. As amostras de sangue foram coletadas duas vezes por semana durante cinco semanas. No conjunto das raças, o EC não influenciou (P>0,05 as concentrações de testosterona (1,8±0,2 vs 1,3±0,2ng/ml e nem a de T4 (52,7±2,8 vs 50,0±2,8ng/ml. Houve declínio (PTo verify the effect of heat stress (HS on plasma testosterone, triiodothyronine (T3, and thyroxine (T4 concentrations, eight Saanen (n=4 and Alpine Brown (n=4 bucks were kept in climate chamber under thermal neutral conditions (13.0ºC to 26.7ºC for 30 days. After a resting period (60 days, the same bucks were submitted to heat stress (23.7ºC to 34.0ºC for another 30 days. To neutralize the seasonal variations of hormonal profiles throughout the period, the photoperiod was controlled every 30 days altering long (16 hours of light and 8 hours of darkness and short days (8 hours of light and 16 hours of darkness. The blood samples were collected twice a week during five weeks. In both breeds, there was no effect of HS (P>0.05 on plasma concentrations of testosterone (1.8±0.2 vs 1.3±0.2ng/ml and T4 (52.7±2.8 vs 50.0±2.8ng/ml. There was a decline (P<0.01 of plasma T3 concentrations (1.3±0.1 vs 1.0±0.1ng/ml after HS treatment, but this reduction was only

  11. Isolation and partial characterization of peripheral blood CD4+ T cell clones expressing γδT cell receptors

    International Nuclear Information System (INIS)

    Kyoizumi, Seishi; Akiyama, Mitoshi; Hirai, Yuko; Kusunoki, Yoichiro.

    1990-06-01

    Rare T cell clones bearing both CD4 and T cell receptors (TCRγ and TCRδ) were obtained from human peripheral blood by cell sorting using anti-CD4 and anti-TCRδ1 antibodies. All the clones established were reactive with anti-TCRγδ1 antibody, whereas only about 20 % of the clones showed reactivity with anti-δTCS1 antibody. Unlike CD4 + T cells bearing TCRαβ, all the clones tested were lectin-dependent and showed CD3 antibody-redirected cytolytic activity. About 60 % exhibited natural killer cell-like activity. Immunoprecipitation analysis of TCRγδ showed that each clone expressed either a disulfide-linked or nondisulfide-linked heterodimer consisting of 37-44 kilodalton TCRγ and TCRδ chains. Southern blot analyses of TCRγ and TCRδ genes revealed some identical rearrangement patterns, suggesting the limited heterogeneity of CD4 + TCRγδ + T cells in peripheral blood. (author)

  12. n – 3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation

    Science.gov (United States)

    Hou, Tim Y.; Monk, Jennifer M.; Fan, Yang-Yi; Barhoumi, Rola; Chen, Yong Q.; Rivera, Gonzalo M.; McMURRAY, David N.; Chapkin, Robert S.

    2013-01-01

    n – 3 PUFA (polyunsaturated fatty acids), i.e. DHA (docosahexaenoic acid), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since PtdIns(4,5)P2 resides in raft domains and DHA can alter the size of rafts, we hypothesized that PtdIns(4,5)P2 and downstream actin remodelling are perturbed by the incorporation of n – 3 PUFA into membranes, resulting in suppressed T-cell activation. CD4+ T-cells isolated from Fat-1 transgenic mice (membranes enriched in n – 3 PUFA) exhibited a 50% decrease in PtdIns(4,5)P2. Upon activation by plate-bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T-cells failed to metabolize PtdIns(4,5)P2. Furthermore, actin remodelling failed to initiate in Fat-1 CD4+ T-cells upon stimulation; however, the defect was reversed by incubation with exogenous PtdIns(4,5)P2. When Fat-1 CD4+ T-cells were stimulated with anti-CD3/anti-CD28-coated beads, WASP (Wiskott–Aldrich syndrome protein) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PtdIns(4,5)P2 metabolism and actin remodelling, were recapitulated in CD4+ T-cells isolated from mice fed on a 4% DHA triacylglycerol-enriched diet. Collectively, these data demonstrate that n – 3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells. PMID:22250985

  13. Seymour Benzer and T4 rII

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 10. Seymour Benzer and T4 rII - Running the Map into the Ground. R Jayaraman. General Article Volume 13 Issue 10 October 2008 pp 898-908. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. Effects of thyroxine (T4) and triiodothyronine (T3) on the thyrotropin (TSH) response to TSH-releasing hormone (TRH) in the rat

    International Nuclear Information System (INIS)

    Boado, R.J.; Ulloa, E.R.; Zaninovich, A.A.

    1982-01-01

    Wistar rats were treated with 7.8 or 260 nmols T4/100 g BW, 1.5 or 260 nmols T3/100 g BW, or saline as control. Twenty minutes later 1 μg TRH/100 g BW was injected iv. Heparinized blood samples were drawn at times 0 and 30 minutes (10 min post-TRH) for determination of plasma TSH, T4 and T3 by RIA. Other group of rats were administered with 150 μCi of 3',5'- 125 I-T4 prepared by iodination of 3,5-diiodothyronine. Thirty minutes later the hypophyses were removed, and chromatographed. Other group of animals were treated with 5 mg of iopanoic acid (IOP)/100 g BW. Thereafter, rats were injected iv with 260 nmols T4 or T3/100 g BW and the TRH-test performed as described above. In the control group there was a 11-fold increase in plasma TSH at 10 minutes post-TRH. In rats treated with 260 nmols T4 the post-TRH increment in plasma TSH was 5+-1-fold (p 125 I-T3 in the hypophyses 30 minutes after 125 I-T4 administration. The present data indicate that T4 is capable of depressing the release of TSH in response to TRH stimulation in normal rats. (M.E.L.) [es

  15. Depletion of naive CD4 T cells by CXCR4-using HIV-1 variants occurs mainly through increased T-cell death and activation

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Otto, Sigrid A.; Hamann, Dörte; Roos, Marijke Th L.; Schuitemaker, Hanneke; de Boer, Rob J.; Miedema, Frank

    2003-01-01

    Objective: Using SCID-Hu mice models and in vitro culture systems, it has been shown that syncytium inducing/CXCR4 using (X4) HIV-1 variants affect thymic function through infection and killing of CXCR4 thymocytes. The effect of X4-emergence on naive, memory and effector T-cell subset kinetics in

  16. Nonsense mutants in the bacteriophage T4D v gene

    Energy Technology Data Exchange (ETDEWEB)

    Minderhout, L van; Grimbergen, J; Groot, B de [Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese; Cohen (J.A.) Instituut voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

    1975-09-01

    Ten UV-sensitive mutants of T4D with the v phenotype were isolated. Of these ten mutants, two are amber and two opal. In UV curves and in photoreactivation and multiplicity reactivation experiments the nonsense mutants show the v phenotype in su/sup -/ hosts and almost the T4/sup +/ phenotype in su/sup +/ hosts. The mutations are located between rl and e and are alleles of v/sub 1/. In crosses with irradiated and non-irradiated phages the recombinant frequency is not reduced by uvs5. Amber uvs5 propagated in CR63 su/sup +/ is with B su/sup -/ just as sensitive to UV as uvs5 propagated in B su/sup -/, which permits the conclusion that the capsid of T4 phage particles does not contain the v gene product.

  17. Human leucocyte antigen class I-redirected anti-tumour CD4+ T cells require a higher T cell receptor binding affinity for optimal activity than CD8+ T cells.

    Science.gov (United States)

    Tan, M P; Dolton, G M; Gerry, A B; Brewer, J E; Bennett, A D; Pumphrey, N J; Jakobsen, B K; Sewell, A K

    2017-01-01

    CD4 + T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4 + T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4 + T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4 + cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4 + and CD8 + T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4 + T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4 + T cells than CD8 + T cells. These results indicate that the CD4 + T cell component of current adoptive therapies using TCRs optimized for CD8 + T cells is below par and that there is room for substantial improvement. © 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

  18. Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

    Science.gov (United States)

    Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

    2017-01-01

    CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

  19. Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection.

    Science.gov (United States)

    Bhattacharyya, Mitra; Madden, Patrick; Henning, Nathan; Gregory, Shana; Aid, Malika; Martinot, Amanda J; Barouch, Dan H; Penaloza-MacMaster, Pablo

    2017-10-01

    CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naive CD4 T cells undergo substantial expansion following infection, but can induce lethal T helper type 1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper cell subsets and were able to improve adaptive immune responses in the context of minimal tissue damage. Our analyses revealed that type I interferon regulates the expansion of primary CD4 T cells, but does not seem to play a critical role in regulating the expansion of secondary CD4 T cells. Strikingly, blockade of type I interferon abrogated lethal inflammation by primary CD4 T cells following viral infection, despite that this treatment increased the numbers of primary CD4 T-cell responses. Altogether, these data demonstrate important aspects of how primary and secondary CD4 T cells are regulated in vivo, and how they contribute to immune protection and immunopathology. These findings are important for rational vaccine design and for improving adoptive T-cell therapies against persistent antigens. © 2017 John Wiley & Sons Ltd.

  20. Psoriasis associated with idiopathic CD4+ T-cell lymphopenia: a regulatory T-cell defect?

    Science.gov (United States)

    Baroudjian, B; Viguier, M; Battistella, M; Beneton, N; Pagès, C; Gener, G; Bégon, E; Bachelez, H

    2014-07-01

    Idiopathic CD4(+) lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established; however, skin dysimmune diseases, including psoriasis, have been scarcely reported up to now. We report herein the severe course of psoriasis in four patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4(+) FoxP3(+) T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model that might also apply to other immune deficiencies associated with psoriasis. © 2014 British Association of Dermatologists.

  1. Interaction of bacteriophage T4 and T7 single-stranded DNA-binding proteins with DNA

    International Nuclear Information System (INIS)

    Shokri, Leila; Williams, Mark C; Rouzina, Ioulia

    2009-01-01

    Bacteriophages T4 and T7 are well-studied model replication systems, which have allowed researchers to determine the roles of many proteins central to DNA replication, recombination and repair. Here we summarize and discuss the results from two recently developed single-molecule methods to determine the salt-dependent DNA-binding kinetics and thermodynamics of the single-stranded DNA (ssDNA)-binding proteins (SSBs) from these systems. We use these methods to characterize both the equilibrium double-stranded DNA (dsDNA) and ssDNA binding of the SSBs T4 gene 32 protein (gp32) and T7 gene 2.5 protein (gp2.5). Despite the overall two-orders-of-magnitude weaker binding of gp2.5 to both forms of DNA, we find that both proteins exhibit four-orders-of-magnitude preferential binding to ssDNA relative to dsDNA. This strong preferential ssDNA binding as well as the weak dsDNA binding is essential for the ability of both proteins to search dsDNA in one dimension to find available ssDNA-binding sites at the replication fork

  2. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; Huang, Y.S.; Chen, Y.F. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Medical Imaging; Kuo, S.H. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; National Taiwan Univ. College of Medicine, Taipei (China). Graduate Inst. of Clinical Medicine; Hong, R.L. [National Taiwan Univ. Hospital, Taipei (China). Div. of Medical Oncology; Ko, J.Y.; Lou, P.J. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Otolaryngology

    2013-12-15

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade {>=} 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  3. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

    International Nuclear Information System (INIS)

    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W.; Huang, Y.S.; Chen, Y.F.; Kuo, S.H.; National Taiwan Univ. College of Medicine, Taipei; Hong, R.L.; Ko, J.Y.; Lou, P.J.

    2013-01-01

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade ≥ 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  4. Enteroantigen-presenting B cells efficiently stimulate CD4(+) T cells in vitro

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Kristensen, Nanna Ny; Claesson, Mogens Helweg

    2011-01-01

    Presentation of enterobacterial antigens by antigen-presenting cells and activation of enteroantigen-specific CD4(+) T cells are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects of such CD4(+) T cells have been thoroughly demonstrated in models...... of colitis. Also, we have previously established an in vitro assay where murine enteroantigen-specific colitogenic CD4(+) CD25(-) T cells are activated by splenocytes pulsed with an enterobacterial extract....

  5. 20 CFR 604.4 - Application-ability to work.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Application-ability to work. 604.4 Section... ELIGIBILITY FOR UNEMPLOYMENT COMPENSATION § 604.4 Application—ability to work. (a) A State may consider an... all or a portion of the week claimed, provided any limitation on his or her ability to work does not...

  6. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Science.gov (United States)

    Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L

    2017-01-01

    Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  7. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Kimberly M Ramonell

    Full Text Available Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  8. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  9. T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology

    Directory of Open Access Journals (Sweden)

    Millard Andrew D

    2010-10-01

    Full Text Available Abstract From genomic sequencing it has become apparent that the marine cyanomyoviruses capable of infecting strains of unicellular cyanobacteria assigned to the genera Synechococcus and Prochlorococcus are not only morphologically similar to T4, but are also genetically related, typically sharing some 40-48 genes. The large majority of these common genes are the same in all marine cyanomyoviruses so far characterized. Given the fundamental physiological differences between marine unicellular cyanobacteria and heterotrophic hosts of T4-like phages it is not surprising that the study of cyanomyoviruses has revealed novel and fascinating facets of the phage-host relationship. One of the most interesting features of the marine cyanomyoviruses is their possession of a number of genes that are clearly of host origin such as those involved in photosynthesis, like the psbA gene that encodes a core component of the photosystem II reaction centre. Other host-derived genes encode enzymes involved in carbon metabolism, phosphate acquisition and ppGpp metabolism. The impact of these host-derived genes on phage fitness has still largely to be assessed and represents one of the most important topics in the study of this group of T4-like phages in the laboratory. However, these phages are also of considerable environmental significance by virtue of their impact on key contributors to oceanic primary production and the true extent and nature of this impact has still to be accurately assessed.

  10. The antimutagenic effect of monoterpenes against UV-irradiation-, 4NQO- and t-BOOH-induced mutagenesis in coli

    Directory of Open Access Journals (Sweden)

    Nikolić Biljana

    2011-01-01

    Full Text Available The aim of this work was to investigate the antimutagenic potential of monoterpenes from sage and basil in Escherichia coli. The mutagenic potential of monoterpenes was pre-screened with Salmonella/microsome reversion assay in strain TA100 and no mutagenic effect was detected. The antimutagenic potential against UV- 4NQO- and t-BOOH induced mutagenesis was evaluated in E. coli K12 and E. coli WP2 by reversion assays. The obtained results indicate that camphor and thujone reduce UV- and 4NQO-induced mutations; myrcene reduces t-BOOH-induced mutations, while eucalyptol and linalool reduce mutagenicity by all tested mutagens. Considering evolutionary conservation of DNA repair and antioxidative protection, the obtained results indicate that further antigenotoxicity studies should be undertaken in eukaryotes.

  11. Copper complex N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone - ({sup 64}Cu)(H2Ac4oT)Cl - internal dosimetry: animal model and human extrapolation

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Josianne L.; Silva, Paulo R.O.; Santos, Raquel G.; Ferreira, Andrea V., E-mail: jlr@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    Thiosemicarbazones have attracted great pharmacological interest because of their biological properties, such as cytotoxic activity against multiple strains of human tumors. Due to the excellent properties of {sup 64}Cu, the copper complex N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone (({sup 64}Cu)(H2Ac4oT)Cl) was developed for tumor detection by positron emission tomography. The radiopharmaceuticals were produced in the nuclear reactor TRIGA-IPR-R1 from CDTN. At the present work, ({sup 64}Cu)(H2Ac4oT)Cl biokinetic data (evaluated in mice bearing Ehrlich tumor) were treated by MIRD formalism to perform Internal Dosimetry studies. Doses in several organs of mice were determinate, as well as in implanted tumor, for ({sup 64}Cu)(H2Ac4oT)Cl. Doses results obtained for animal model were extrapolated to humans assuming a similar concentration ratio among various tissues between mouse and human. In the extrapolation, it was used human organ masses from Cristy/Eckerman phantom. Both penetrating and non-penetrating radiation from {sup 64}Cu in the tissue were considered in dose calculations. (author)

  12. Sensor Compendium - A Snowmass Whitepaper-

    Energy Technology Data Exchange (ETDEWEB)

    Artuso, M. [Syracuse Univ., NY (United States); Battaglia, M. [Univ. of California, Santa Cruz, CA (United States); Bolla, G. [Purdue Univ., West Lafayette, IN (United States); Bortoletto, D. [Purdue Univ., West Lafayette, IN (United States); Caberera, B. [Stanford Univ., CA (United States); Carlstrom, J E [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Chang, C. L. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Cooper, W. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Da Via, C. [Univ. of Manchester (United Kingdom); Demarteau, M. [Argonne National Lab. (ANL), Argonne, IL (United States); Fast, J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Frisch, H. [Univ. of Chicago, IL (United States), et al.

    2013-10-01

    Sensors play a key role in detecting both charged particles and photons for all three frontiers in Particle Physics. The signals from an individual sensor that can be used include ionization deposited, phonons created, or light emitted from excitations of the material. The individual sensors are then typically arrayed for detection of individual particles or groups of particles. Mounting of new, ever higher performance experiments, often depend on advances in sensors in a range of performance characteristics. These performance metrics can include position resolution for passing particles, time resolution on particles impacting the sensor, and overall rate capabilities. In addition the feasible detector area and cost frequently provides a limit to what can be built and therefore is often another area where improvements are important. Finally, radiation tolerance is becoming a requirement in a broad array of devices. We present a status report on a broad category of sensors, including challenges for the future and work in progress to solve those challenges.

  13. Polymerized-Type I Collagen Induces Upregulation of Foxp3-Expressing CD4 Regulatory T Cells and Downregulation of IL-17-Producing CD4+ T Cells (Th17 Cells in Collagen-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Janette Furuzawa-Carballeda

    2012-01-01

    Full Text Available Previous studies showed that polymerized-type I collagen (polymerized collagen exhibits potent immunoregulatory properties. This work evaluated the effect of intramuscular administration of polymerized collagen in early and established collagen-induced arthritis (CIA in mice and analyzed changes in Th subsets following therapy. Incidence of CIA was of 100% in mice challenged with type II collagen. Clinimorphometric analysis showed a downregulation of inflammation after administration of all treatments (P<0.05. Histological analysis showed that the CIA-mice group had extensive bone erosion, pannus and severe focal inflammatory infiltrates. In contrast, there was a remarkable reduction in the severity of arthritis in mice under polymerized collagen, methotrexate or methotrexate/polymerized collagen treatment. Polymerized Collagen but not methotrexate induced tissue joint regeneration. Polymerized Collagen and methotrexate/polymerized collagen but not methotrexate alone induces downregulation of CD4+/IL17A+ T cells and upregulation of Tregs and CD4+/IFN-γ+ T cells. Thus, Polymerized Collagen could be an effective therapeutic agent in early and established rheumatoid arthritis by exerting downregulation of autoimmune inflammation.

  14. The ThPOK transcription factor differentially affects the development and function of self-specific CD8(+) T cells and regulatory CD4(+) T cells.

    Science.gov (United States)

    Twu, Yuh-Ching; Teh, Hung-Sia

    2014-03-01

    The zinc finger transcription factor ThPOK plays a crucial role in CD4 T-cell development and CD4/CD8 lineage decision. In ThPOK-deficient mice, developing T cells expressing MHC class II-restricted T-cell receptors are redirected into the CD8 T-cell lineage. In this study, we investigated whether the ThPOK transgene affected the development and function of two additional types of T cells, namely self-specific CD8 T cells and CD4(+) FoxP3(+) T regulatory cells. Self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11 and proliferation in response to either IL-2 or IL-15. The ThPOK transgene converted these self-specific CD8 T cells into CD4 T cells. The converted CD4(+) T cells are no longer self-reactive, lose the characteristics of self-specific CD8 T cells, acquire the properties of conventional CD4 T cells and survive poorly in peripheral lymphoid organs. By contrast, the ThPOK transgene promoted the development of CD4(+) FoxP3(+) regulatory T cells resulting in an increased recovery of CD4(+) FoxP3(+) regulatory T cells that expressed higher transforming growth factor-β-dependent suppressor activity. These studies indicate that the ThPOK transcription factor differentially affects the development and function of self-specific CD8 T cells and CD4(+) FoxP3(+) regulatory T cells. © 2013 John Wiley & Sons Ltd.

  15. Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Kasprzycka, Monika; Zhang, Qian; Witkiewicz, Agnieszka

    2008-01-01

    In this study, we demonstrate that malignant mature CD4(+) T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed...... that FOXP3-expressing cells were common among the CD7-negative enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate...

  16. Functional correlates of TSH, fT3 and fT4 in Alzheimer disease: a F-18 FDG PET/CT study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Ursini, Francesco; Fiorentini, Alessandro; Barbagallo, Gaetano; Martorana, Alessandro; Koch, Giacomo; Tavolozza, Mario; Schillaci, Orazio

    2017-07-24

    The present study was aimed to investigate the relationships between thyroid stimulating hormone (TSH), freeT3 (fT3) and freeT4 (fT4) and brain glucose consumption as detectable by means of 2-deoxy-2-(F-18) fluoro-D-glucose (F-18 FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in a selected population with Alzheimer disease (AD). We evaluated 87 subjects (37 males and 50 females, mean age 70 (±6) years old) with AD. All of them were subjected to TSH, fT3 and fT4 assay and to cerebrospinal fluid amyloid (Aβ1-42) and tau [phosphorylated-tau (p-tau) and total-tau (t-tau)] assay prior PET/CT examination. Values for TSH, fT3 and fT4 were in the normal range. The relationships were evaluated by means of statistical parametric mapping (SPM8) using age, sex, MMSE, scholarship and CSF values of amyloid and tau as covariates. We found a significant positive correlation between TSH values and cortical glucose consumption in a wide portion of the anterior cingulate cortex bilaterally (BA32) and left frontal lobe (BA25) (p FWE-corr <0.001; p FDRcorr <0.000; cluster extent 66950). No significant relationships were found between cortical F-18 FDG uptake and T3 and T4 serum levels. The results of our study suggest that a cortical dysfunction in anterior cingulate and frontal lobes may affect serum values of TSH in AD patients.

  17. P-T and T-x projections of phase diagram of CsF-ZrF4 system

    International Nuclear Information System (INIS)

    Karasev, N.M.; Korenev, Yu.M.; Sidorov, L.N.

    1980-01-01

    The CsF-ZrF 4 system has been investigated by the Knudsen effusion method and mass-spectral analysis of vaporization products. A molecular composition of vapour was determined. CsF, Cs 2 F 2 , ZrF 4 , Cs 2 ZrF 6 , CsZrF 5 , CsZr 2 F 9 molecules were found in the saturated vapour of the system. Heats of phase transitions and partial pressures of the molecules detected were determined depending on the melt compositions. Dissociation enthalpies of complex molecules were calculated. P-T and T-x projections of the state diagram of the CsF-ZrF 4 system were constructed

  18. When aging reaches CD4+ T-cells: phenotypic and functional changes

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moro-García

    2013-05-01

    Full Text Available Beyond midlife, the immune system shows aging features and its defensive capability becomes impaired, by a process known as immunosenescence that involves many changes in the innate and adaptive responses. Innate immunity seems to be better preserved globally, while the adaptive immune response exhibits profound age-dependent modifications. Elderly people display a decline in numbers of naïve T-cells in peripheral blood and lymphoid tissues, while, in contrast, their proportion of highly differentiated effector and memory T-cells, such as the CD28null T-cells, increases markedly. Naïve and memory CD4+ T-cells constitute a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T-cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T-cells. Homeostatic control mechanisms are very effective at maintaining a large and diverse subset of naïve CD4+ T-cells throughout life, but although later than in CD8+T-cell compartment, these mechanisms ultimately fail with age.

  19. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

    Science.gov (United States)

    Milush, Jeffrey M.; Mir, Kiran D.; Sundaravaradan, Vasudha; Gordon, Shari N.; Engram, Jessica; Cano, Christopher A.; Reeves, Jacqueline D.; Anton, Elizabeth; O’Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S.; Brenchley, Jason M.; Else, James G.; Silvestri, Guido; Sodora, Donald L.

    2011-01-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species. PMID:21317533

  20. Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

    Science.gov (United States)

    Raué, Hans-Peter; Slifka, Mark K

    2007-05-01

    Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

  1. T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible.

    Science.gov (United States)

    Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Schwab, Nicholas; Wiendl, Heinz

    2009-08-01

    CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA-G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T cell proliferation in vitro, suggesting their role in immune regulation. We here characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous HLA-G(neg) T(resp) function. Using a suppression system free of APC, we demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg) T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression is independent of cell-cell contact and is reversible, as the removal of HLA-G(pos) T(reg) from the established coculture restored the proliferative capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression critically depends on the secretion of IL-10 but not TGF-beta.

  2. Changes in Reactivity In Vitro of CD4+CD25+ and CD4+CD25− T Cell Subsets in Transplant Tolerance

    Science.gov (United States)

    Hall, Bruce M.; Robinson, Catherine M.; Plain, Karren M.; Verma, Nirupama D.; Tran, Giang T.; Nomura, Masaru; Carter, Nicole; Boyd, Rochelle; Hodgkinson, Suzanne J.

    2017-01-01

    Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4+CD25+ T cells, yet in many models, proliferation of CD4+ T cells from hosts tolerant to specific-alloantigen in vitro is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4+, CD4+CD25+, and CD4+CD25− T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4+ T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4+CD25− T cells was greater than naïve CD4+ T cells. In contrast, proliferation of CD4+CD25− T cells from tolerant hosts to specific-donor PVG was not greater than CD4+ T cells, whereas their response to Lewis and self-DA was greater than CD4+ T cells. Paradoxically, CD4+CD25+ T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4+CD25+ T cells proliferate to both PVG and Lewis but not to self-DA. CD4+CD25+ T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4+CD25+ T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4+CD25+ T cells that mediate transplant tolerance depend on IFN−γ or IL-5 from alloactivated Th1 and Th2 cells. PMID:28878770

  3. Clinical significance of two-step magnetic radioimmunoassay for determining serum free T3 and free T4

    International Nuclear Information System (INIS)

    Chen Bing

    1996-01-01

    The concentrations of the serum free T 3 (FT 3 ), free T 4 (FT 4 ), total triodothyronine (TT 3 ), total thyroxine (TT 4 ) and thyrotropin (TSH) are determined for 355 cases of normal persons, pregnant women and various thyropathetic patients. The normal values of FT 3 and FT 4 are 2.0-8.5 pmol/l, and 9.5-26.5 pmol/l, respectively. Neither FT 3 nor FT 4 is affected by the thyroxine combined with globulin (TBG), which is of unique diagnostic value for those with variable TBG (such as pregnant women hyperthyroidism, hypothyroidism, etc.), FT 3 and FT 4 are the most sensitive indices for diagnosis of hyperthyroidism, and hypothyroidism, respectively. In addition, FT 3 and FT 4 can greatly contribute to the observation of curative effectiveness under treatment

  4. IL-17-Expressing CD4+ and CD8+ T Lymphocytes in Human Toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Jéssica Líver Alves Silva

    2014-01-01

    Full Text Available This study aimed to measure the synthesis of Th1 and Th2 cytokines by mononuclear cells after culture with live T. gondii and identified Th17 (CD4+ and Tc17 (CD8+ cells in toxoplasma-seronegative and toxoplasma-seropositive parturient and nonpregnant women. Cytometric bead arrays were used to measure cytokine levels (IL-2, TNF-α, IFN-γ, IL-4, IL-5, and IL-10; immunophenotyping was used to characterize Th17 and Tc17 cells, and the cells were stained with antibodies against CD4+ and CD8+ T cells expressing IL-17. The addition of tachyzoites to cell cultures induced the synthesis of IL-5, IL-10, and TNF-α by cells from seronegative parturient women and of IL-5 and IL-10 by cells from seropositive, nonpregnant women. We observed a lower level of IL-17-expressing CD4+ and CD8+ T lymphocytes in cultures of cells from seronegative and seropositive parturient and nonpregnant women that were stimulated with tachyzoites, whereas analysis of the CD4+ and CD8+ T cell populations showed a higher level of CD4+ T cells compared with CD8+ T cells. These results suggest that the cytokine pattern and IL-17-expressing CD4+ and CD8+ T lymphocytes may have important roles in the inflammatory response to T. gondii, thus contributing to the maintenance of pregnancy and control of parasite invasion and replication.

  5. Establishment of reference CD4+ T cell values for adult Indian population

    Directory of Open Access Journals (Sweden)

    Ray Krishnangshu

    2011-10-01

    Full Text Available Abstract Background CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. Methods A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre healthy participants were enrolled in the study. The ratio of male (N = 645 to female (N = 561 of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS, version 15 and Prism software version 5. Results The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. Conclusion The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.

  6. [Changes of CD(4)(+)Foxp3(+) regulatory T cells and CD(4)(+)IL-17(+)T cells in cigarette smoke-exposed rats].

    Science.gov (United States)

    Meng, Jing-jing; Zhong, Xiao-ning; Bai, Jing; He, Zhi-yi; Zhang, Jian-quan; Huang, Qiu-pin

    2012-01-01

    To evaluate the changes of CD(4)(+)IL-17(+) T (Th17) and CD(4)(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF), and therefore to explore the role of Th17 and Treg in cigarette smoke-induced airway inflammation/COPD in rats. Forty male Wistar rats were randomly divided into 4 groups: a 12 wk smoke-exposure group, a 24 wk smoke-exposure group, a 12 wk control group and a 24 wk control group (n = 10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts. IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17(+) T and CD(4)(+)Foxp3(+) Treg in peripheral blood and BALF were determined by flow cytometry. The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 12 wk smoke-exposure group and the 24 wk smoke-exposure group in serum [(52.6 ± 1.8) ng/L, (75.4 ± 6.0) ng/L] and BALF [(78.1 ± 5.8) ng/L, (95.0 ± 6.8) ng/L] compared with the 12 wk control group [(40.0 ± 3.2)ng/L, (54.5 ± 4.6) ng/L] and the 24 wk control group [(36.7 ± 3.2) ng/L, (53.9 ± 3.7) ng/L], all P cells and macrophages (r = 0.512, 0.543, all P cells and an increase of inflammatory cytokines were evident in airway inflammation of cigarette smoke-exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in cigarette smoke-induced airway inflammation in rats.

  7. Whole transcriptome analysis for T cell receptor-affinity and IRF4-regulated clonal expansion of T cells

    Directory of Open Access Journals (Sweden)

    Wei Shi

    2014-12-01

    Full Text Available Clonal population expansion of T cells during an immune response is dependent on the affinity of the T cell receptor (TCR for its antigen [1]. However, there is little understanding of how this process is controlled transcriptionally. We found that the transcription factor IRF4 was induced in a manner dependent on TCR-affinity and was critical for the clonal expansion and maintenance of effector function of antigen-specific CD8+ T cells. We performed a genome-wide expression profiling experiment using RNA sequencing technology (RNA-seq to interrogate global expression changes when IRF4 was deleted in CD8+ T cells activated with either a low or high affinity peptide ligand. This allowed us not only to determine IRF4-dependent transcriptional changes but also to identify transcripts dependent on TCR-affinity [2]. Here we describe in detail the analyses of the RNA-seq data, including quality control, read mapping, quantification, normalization and assessment of differential gene expression. The RNA-seq data can be accessed from Gene Expression Omnibus database (accession number GSE49929.

  8. Immunoregulatory T Cells May Be Involved in Preserving CD4 T Cell Counts in HIV-Infected Long-Term Nonprogressors and Controllers

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Ronit, Andreas; Hartling, Hans J

    2014-01-01

    BACKGROUND: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell...... of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors....... counts in controllers and in LTNPs. METHODS: Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17...

  9. 4+ T Cells: A Novel IL-17-Producing γδ T Subsets during the Early Phase of Chlamydial Airway Infection in Mice

    Directory of Open Access Journals (Sweden)

    Li-da Sun

    2018-01-01

    Full Text Available Our previous studies showed that γδ T cells provided immune protection against Chlamydial muridarum (Cm, an obligate intracellular strain of chlamydia trachomatis, lung infection by producing abundant IL-17. In this study, we investigated the proliferation and activation of lung γδ T cell subsets, specifically the IL-17 and IFNγ production by them following Cm lung infection. Our results found that five γδ T cell subsets, Vγ1+ T, Vγ2+ T, Vγ4+ T, Vγ5+ T, and Vγ6+ T, expressed in lungs of naïve mice, while Cm lung infection mainly induced the proliferation and activation of Vγ4+ T cells at day 3 p.i., following Vγ1+ T cells at day 7 p.i. Cytokine detection showed that Cm lung infection induced IFNγ secretion firstly by Vγ4+ T cells at very early stage (day 3 and changed to Vγ1+ T cells at midstage (day 7. Furthermore, Vγ4+ T cell is the main γδ T cell subset that secretes IL-17 at the very early stage of Cm lung infection and Vγ1+ T cell did not secrete IL-17 during the infection. These findings provide in vivo evidence that Vγ4+T cells are the major IL-17 and IFNγ-producing γδ T cell subsets at the early period of Cm lung infection.

  10. Innate-like CD4 T cells selected by thymocytes suppress adaptive immune responses against bacterial infections

    OpenAIRE

    Qiao, Yu; Gray, Brian M.; Sofi, Mohammed H.; Bauler, Laura D.; Eaton, Kathryn A.; O'Riordan, Mary X. D.; Chang, Cheong-Hee

    2011-01-01

    We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T ce...

  11. Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling.

    Science.gov (United States)

    Sun, Xuan; Liu, Suoning; Wang, Daguang; Zhang, Yang; Li, Wei; Guo, Yuchen; Zhang, Hua; Suo, Jian

    2017-02-28

    Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, β-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of β-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.

  12. CDC Vital Signs–Blood Pressure Medicines Don’t Work If People Don’t Take Them

    Centers for Disease Control (CDC) Podcasts

    2016-09-13

    Blood pressure medicines don’t work if people don’t take them. Learn how health care systems can work with patients to make taking medicines easier.  Created: 9/13/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/13/2016.

  13. Working memory capacity differentially influences responses to tDCS and HD-tDCS in a retro-cue task.

    Science.gov (United States)

    Gözenman, Filiz; Berryhill, Marian E

    2016-08-26

    There is growing interest in non-invasive brain stimulation techniques. A drawback is that the relationship between stimulation and cognitive outcomes for various tasks are unknown. Transcranial direct current stimulation (tDCS) provides diffuse current spread, whereas high-definition tDCS (HD-tDCS) provides more targeted current. The direction of behavioral effects after tDCS can be difficult to predict in cognitive realms such as attention and working memory (WM). Previously, we showed that in low and high WM capacity groups tDCS modulates performance in nearly equal and opposite directions on a change detection task, with improvement for the high capacity participants alone. Here, we used the retro-cue paradigm to test attentional shifting among items in WM to investigate whether WM capacity (WMC) predicted different behavioral consequences during anodal tDCS or HD-tDCS to posterior parietal cortex (PPC). In two experiments, with 24 participants each, we used different stimulus categories (colored circles, letters) and stimulation sites (right, left PPC). The results showed a significant (Experiment 1) or trending (Experiment 2) WMC x stimulation interaction. Compared to tDCS, after HD-tDCS the retro-cueing benefit was significantly greater for the low WMC group but numerically worse for the high WMC group. These data highlight the importance of considering group differences when using non-invasive neurostimulation techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Interleukin 4: signalling mechanisms and control of T cell differentiation.

    Science.gov (United States)

    Paul, W E

    1997-01-01

    Interleukin 4 (IL-4) is a pleiotropic type I cytokine that controls both growth and differentiation among haemopoietic and non-haemopoietic cells. Its receptor is a heterodimer. One chain, the IL-4R alpha chain, binds IL-4 with high affinity and determines the nature of the biochemical signals that are induced. The second chain, gamma c, is required for the induction of such signals. IL-4-mediated growth depends upon activation events that involve phosphorylation of Y497 of IL-4R alpha, leading to the binding and phosphorylation of 4PS/IRS-2 in haemopoietic cells and of IRS-1 in non-haemopoietic cells. By contrast, IL-4-mediated differentiation events depend upon more distal regions of the IL-4R alpha chain that include a series of STAT-6 binding sites. The distinctive roles of these receptor domains was verified by receptor-reconstruction experiments. The 'growth' and 'differentiation' domains of the IL-4R alpha chain, independently expressed as chimeric structures with a truncated version of the IL-2R beta chain, were shown to convey their functions to the hybrid receptor. The critical role of STAT-6 in IL-4-mediated gene activation and differentiation was made clear by the finding that lymphocytes from STAT-6 knockout mice are strikingly deficient in these functions but have retained the capacity to grow, at least partially, in response to IL-4. IL-4 plays a central role in determining the phenotype of naive CD4+ T cells. In the presence of IL-4, newly primed naive T cells develop into IL-4 producers while in its absence they preferentially become gamma-interferon (IFN-gamma) producers. Recently, a specialized subpopulation of T cells, CD4+/NK1.1+ cells, has been shown to produce large amounts of IL-4 upon stimulation. Two examples of mice with deficiencies in these cells are described--beta 2-microglobulin knockout mice and SJL mice. Both show defects in the development of IL-4-producing cells and in the increase in serum IgE in response to stimulation with the

  15. Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

    Science.gov (United States)

    Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

    2017-05-01

    Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin

  16. Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB.

    Science.gov (United States)

    Li, Shiqi; Zhang, Jiasi; Wang, Meiling; Fu, Gang; Li, Yunyan; Pei, Li; Xiong, Zhouxing; Qin, Dabing; Zhang, Rui; Tian, Xiaobo; Wei, Zhihao; Chen, Run; Chen, Xuejiao; Wan, Jia; Chen, Jun; Wei, Xia; Xu, Yanmin; Zhang, Pei; Wang, Ping; Peng, Xi; Yang, Sainan; Shen, Junjie; Yang, Zhi; Chen, Jieping; Qian, Cheng

    2018-04-10

    T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level. © 2018 John Wiley & Sons Ltd.

  17. Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina

    Directory of Open Access Journals (Sweden)

    Marta E. Martinuzzo

    2012-02-01

    Full Text Available La trombocitopenia inducida por heparina (HIT es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4-heparina (HPIA. La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica. El índice de las 4T (índice 4T puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS. La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001. Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001. Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017. En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.

  18. Increased autophagy in CD4(+) T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance

    NARCIS (Netherlands)

    van Loosdregt, Jorg; Rossetti, Maura; Spreafico, Roberto; Moshref, Maryam; Olmer, Merissa; Williams, Gary W; Kumar, Pavanish; Copeland, Dana; Pischel, Ken; Lotz, Martin; Albani, Salvatore

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4(+) T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4(+) T cells in the autoimmune

  19. Serum TBG and T4 concentration in non-thyroidal diseases

    International Nuclear Information System (INIS)

    Sasaki, Y.; Tobari, C.; Sekita, N.; Onodera, Y.; Asazu, M.; Someya, K.

    1983-01-01

    Routinely available radioassay kits have recently enabled the measurement of serum concentrations of thyroxine binding globulin (TBG) and thyroxine (T 4 ), both total (TT 4 ) and free (FT 4 ) in various disease conditions. Serum TBG and T 4 level were measured in variety of non-thyroidal diseases, of which significance was evaluated in comparison with that in thyroidal diseases. Abnormal serum TBG concentrations in various non-thyroidal diseases and pregnancy result in abnormal serum TT 4 levels, which may cause difficulty in differentiation of these conditions from hyper- or hypothyroidal states. Serum FT 4 levels give better indicator than TT 4 , though the difference among RIA kits are considerably large. However, measurement of serum FT 4 levels alone is not sufficient to distinguish non-thyroidal disease from thyroidal diseases with abnormal thyroidal function. The differentiation has to be based on the combination of clinical findings and results of multiple thyroidal function tests

  20. A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Daniela Santoro Rosa

    Full Text Available T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+ T cells are important for the generation and maintenance of functional CD8(+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18, capable of eliciting broad CD4(+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+/CD8(+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+ and CD8(+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2 simultaneously in response to HIV-1 peptides. For CD4(+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2. The vaccine also generated long-lived central and effector memory CD4(+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+ T cells and antibody responses- elicited by other HIV immunogens.

  1. In-Depth Analysis of Citrulline Specific CD4 T-Cells in Rheumatoid Arthritis

    Science.gov (United States)

    2017-01-01

    AWARD NUMBER: W81XWH-15-1-0004 TITLE: In-Depth Analysis of Citrulline-Specific CD4 T - Cells in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...NOTES 14. ABSTRACT The goal of this project is to test the hypothesis that cit-specific CD4 T cells present in rheumatoid arthritis (RA) patients

  2. Methionine enkephalin (MENK) inhibits tumor growth through regulating CD4+Foxp3+ regulatory T cells (Tregs) in mice.

    Science.gov (United States)

    Li, Xuan; Meng, Yiming; Plotnikoff, Nicolas P; Youkilis, Gene; Griffin, Noreen; Wang, Enhua; Lu, Changlong; Shan, Fengping

    2015-01-01

    Methionine enkephalin (MENK), an endogenous neuropeptide, plays an crucial role in both neuroendocrine and immune systems. CD4+Foxp3+ regulatory T cells (Tregs) are identified as a major subpopulation of T lymphocytes in suppressing immune system to keep balanced immunity. The aim of this research work was to elucidate the mechanisms via which MENK interacts with Tregs in cancer situation. The influence of MENK on transforming growth factor-β (TGF-β) mediated conversion from naïve CD4+CD25- T cells to CD4+CD25+ Tregs was determined and the data from flow cytometry (FCM) analysis indicated that MENK effectively inhibited the expression of Foxp3 during the process of TGF-βinduction. Furthermore, this inhibiting process was accompanied by diminishing phosphorylation and nuclear translocation of Smad2/3, confirmed by western blot (WB) analysis and immunofluorescence (IF) at molecular level. We established sarcoma mice model with S180 to investigate whether MENK could modulate Tregs in tumor circumstance. Our findings showed that MENK delayed the development of tumor in S180 tumor bearing mice and down-regulated level of Tregs. Together, these novel findings reached a conclusion that MENK could inhibit Tregs activity directly and retard tumor development through down-regulating Tregs in mice. This work advances the deepening understanding of the influence of MENK on Tregs in cancer situation, and relation of MENK with immune system, supporting the implication of MENK as a new strategy for cancer immunotherapy.

  3. T R Ramadas

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. T R Ramadas. Articles written in Resonance – Journal of Science Education. Volume 4 Issue 7 July 1999 pp 79-82 Research News. The Work of the Fields Medallists: 1998 - Maxim Kontsevich · T R Ramadas · More Details Fulltext PDF ...

  4. Production of antisera and development of radioimmunoassay for serum T3, T4, and ferritin

    Energy Technology Data Exchange (ETDEWEB)

    Elhag, Omer Mohamed Abdalla [Department of Biochemistry, Faculty of Veterinary Science, University of Khartoum, Khartoum (Sudan)

    1998-05-01

    In this study twelve local rabbits and sixteen New-zealand rabbits were subjected to immunization against T3 and T4 immunogens. Two local sheep (ovis aris) were immunized against human liver ferritin. The T3 and T4 immunogens were prepared by conjugation of the haptens to carrier proteins (bovine serum albumin ``BSA`` and horse serum protein ``HSP``), using water soluble carboiimide as coupling agent. The local and New-zealand rabbits were immunized against these conjugates emulsified in freund`s complete adjuvant (FCA) in the first and second injections, and emulsified in freund`s incomplete adjuvant (FIA) in the following injections. The blood samples obtained from rabbits after each injection were tested for antibodies as well as for the effect of immunization on rabbits biochemical and haematological parameters. The blood samples obtained from sheep were tested for anti-ferritin antibodies using crude antiserum, then this antiserum was purified using ammonium sulphate. A part of it was adsorbed physically onto polystyrene beads while the other part was linked chemically to magnitisable particles inorder to develop to IRMAs. The purified antiferritin antibody was diluted 200,000 folds before being coated to polystyrene beads, and different dilutions were tried with coupling to magnetic solid phase. Optimization and validation procedures for the two IRMAs ferritin were performed. The results obtained showed poor response of rabbits to immunization against T3 and T4 immunogen conjugates, where the percent bound (B%) of tracer with the antibody ranged from (0.0-22%) for local rabbits using charcoal seperation technique, and (0.0-2.9%) using second antibody precipitation technique. The B% for the antiserum obtained from New-zealand rabbits ranged from (0.0-18.1) using second antibody precipitation technique. Serum T3, T4 and TSH of the immunized rabbits were measured and found to be not significantly different form the controls (p=0.2211, 0.098, 0.35 respectively

  5. Production of antisera and development of radioimmunoassay for serum T3, T4, and ferritin

    International Nuclear Information System (INIS)

    Elhag, Omer Mohamed Abdalla

    1998-05-01

    In this study twelve local rabbits and sixteen New-zealand rabbits were subjected to immunization against T3 and T4 immunogens. Two local sheep (ovis aris) were immunized against human liver ferritin. The T3 and T4 immunogens were prepared by conjugation of the haptens to carrier proteins (bovine serum albumin ''BSA'' and horse serum protein ''HSP''), using water soluble carboiimide as coupling agent. The local and New-zealand rabbits were immunized against these conjugates emulsified in freund's complete adjuvant (FCA) in the first and second injections, and emulsified in freund's incomplete adjuvant (FIA) in the following injections. The blood samples obtained from rabbits after each injection were tested for antibodies as well as for the effect of immunization on rabbits biochemical and haematological parameters. The blood samples obtained from sheep were tested for anti-ferritin antibodies using crude antiserum, then this antiserum was purified using ammonium sulphate. A part of it was adsorbed physically onto polystyrene beads while the other part was linked chemically to magnitisable particles inorder to develop to IRMAs. The purified antiferritin antibody was diluted 200,000 folds before being coated to polystyrene beads, and different dilutions were tried with coupling to magnetic solid phase. Optimization and validation procedures for the two IRMAs ferritin were performed. The results obtained showed poor response of rabbits to immunization against T3 and T4 immunogen conjugates, where the percent bound (B%) of tracer with the antibody ranged from (0.0-22%) for local rabbits using charcoal seperation technique, and (0.0-2.9%) using second antibody precipitation technique. The B% for the antiserum obtained from New-zealand rabbits ranged from (0.0-18.1) using second antibody precipitation technique. Serum T3, T4 and TSH of the immunized rabbits were measured and found to be not significantly different form the controls (p=0.2211, 0.098, 0.35 respectively

  6. Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4(+) T cells.

    Science.gov (United States)

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Reisfeld, Brad; Zurlinden, Todd J; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Cooney, Craig A

    2016-05-01

    Autoimmune disease and CD4(+) T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4(+) T cells as a possible mechanism of immunotoxicity. Naive and effector/memory CD4(+) T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4(+) T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. TCE increased epigenetic drift of specific CpG sites in CD4(+) T cells.

  7. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

    LENUS (Irish Health Repository)

    Adrees, M

    2012-02-01

    CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

  8. Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells

    Science.gov (United States)

    Muraro, Elena; Merlo, Anna; Martorelli, Debora; Cangemi, Michela; Dalla Santa, Silvia; Dolcetti, Riccardo; Rosato, Antonio

    2017-01-01

    CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors. PMID:28289418

  9. Expression and Characterization of Human β-1, 4-Galactosyltransferase 1 (β4GalT1) Using Silkworm–Baculovirus Expression System

    KAUST Repository

    Morokuma, Daisuke

    2017-03-24

    Baculovirus expression vector system (BEVS) is widely known as a mass-production tool to produce functional recombinant glycoproteins except that it may not be always suitable for medical practice due to the differences in the structure of N-linked glycans between insects and mammalian. Currently, various approaches have been reported to alter N-linked glycan structures of glycoproteins derived from insects into terminally sialylated complex-type N-glycans. In the light of those studies, we also proposed in vitro maturation of N-glycan with mass-produced and purified glycosyltransferases by silkworm–BEVS. β-1,4-Galactosyltransferase 1 (β4GalT1) is known as one of type II transmembrane enzymes that transfer galactose in a β-1, 4 linkage to accepter sugars, and a key enzyme for further sialylation of N-glycans. In this study, we developed a large-scale production of recombinant human β4GalT1 (rhβ4GalT1) with N- or C-terminal tags in silkworm–BEVS. We demonstrated that rhβ4GalT1 is N-glycosylated and without mucin-type glycosylation. Interestingly, we found that purified rhβ4GalT1 from silkworm serum presented higher galactosyltransferase activity than that expressed from cultured mammalian cells. We also validated the UDP-galactose transferase activity of produced rhβ4GalT1 proteins by using protein subtracts from silkworm silk gland. Taken together, rhβ4GalT1 from silkworms can become a valuable tool for producing high-quality recombinant glycoproteins with mammalian-like N-glycans.

  10. CD4 T cell activation and disease activity at onset of multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C

    2004-01-01

    We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  11. Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.

    Directory of Open Access Journals (Sweden)

    Yoshihisa Yamano

    Full Text Available BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1 is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL. The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS: Here, we demonstrate that CD4(+CD25(+CCR4(+ T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2, Th17, and regulatory T (Treg cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+CD25(+CCR4(+ T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+CD25(+CCR4(+Foxp3(- T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS: We have defined a unique T cell subset--IFN-gamma(+CCR4(+CD4(+CD25(+ T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system.

  12. Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Shicheng Su; Ling Lin; Yunjie Zeng; Nengtai Ouyang; Xiuying Cui; Herui Yao; Fengxi Su; Jian-dong Huang; Judy Lieberman; Qiang Liu; Erwei Song; Jianyou Liao; Jiang Liu; Di Huang; Chonghua He; Fei Chen; LinBing Yang; Wei Wu; Jianing Chen

    2017-01-01

    The origin of tumor-infiltrating Tregs,critical mediators of tumor immunosuppression,is unclear.Here,we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires,while hardly overlap with circulating Tregs,suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs.Furthermore,the abundance of naive CD4+ T cells and Tregs is closely correlated,both indicating poor prognosis for breast cancer patients.Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCLl8-producing macrophages.Moreover,adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner.In human breast cancer xenografts in humanized mice,blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3,a CCL18 receptor,significantly reduces intratumoral Tregs and inhibits tumor progression.These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ.Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy.

  13. Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

    Science.gov (United States)

    Su, Shicheng; Liao, Jianyou; Liu, Jiang; Huang, Di; He, Chonghua; Chen, Fei; Yang, LinBing; Wu, Wei; Chen, Jianing; Lin, Ling; Zeng, Yunjie; Ouyang, Nengtai; Cui, Xiuying; Yao, Herui; Su, Fengxi; Huang, Jian-dong; Lieberman, Judy; Liu, Qiang; Song, Erwei

    2017-01-01

    The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ. Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy. PMID:28290464

  14. The E. coli Global Regulator DksA Reduces Transcription during T4 Infection

    Directory of Open Access Journals (Sweden)

    Jennifer Patterson-West

    2018-06-01

    Full Text Available Bacteriophage T4 relies on host RNA polymerase to transcribe three promoter classes: early (Pe, requires no viral factors, middle (Pm, requires early proteins MotA and AsiA, and late (Pl, requires middle proteins gp55, gp33, and gp45. Using primer extension, RNA-seq, RT-qPCR, single bursts, and a semi-automated method to document plaque size, we investigated how deletion of DksA or ppGpp, two E. coli global transcription regulators, affects T4 infection. Both ppGpp0 and ΔdksA increase T4 wild type (wt plaque size. However, ppGpp0 does not significantly alter burst size or latent period, and only modestly affects T4 transcript abundance, while ΔdksA increases burst size (2-fold without affecting latent period and increases the levels of several Pe transcripts at 5 min post-infection. In a T4motAam infection, ΔdksA increases plaque size and shortens latent period, and the levels of specific middle RNAs increase due to more transcription from Pe’s that extend into these middle genes. We conclude that DksA lowers T4 early gene expression. Consequently, ΔdksA results in a more productive wt infection and ameliorates the poor expression of middle genes in a T4motAam infection. As DksA does not inhibit Pe transcription in vitro, regulation may be indirect or perhaps requires additional factors.

  15. Understanding the slow depletion of memory CD4+ T cells in HIV infection.

    Directory of Open Access Journals (Sweden)

    Andrew Yates

    2007-05-01

    Full Text Available The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4(+ T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a "runaway" decline of memory CD4(+ T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using mathematical models.Using simple mathematical models of the dynamics of T cell homeostasis and proliferation, we find that this mechanism fails to explain the time scale of CD4(+ memory T cell loss. Instead it predicts the rapid attainment of a stable set point, so other mechanisms must be invoked to explain the slow decline in CD4(+ cells.A runaway cycle in which elevated CD4(+ T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4(+ memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion.

  16. Antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction

    International Nuclear Information System (INIS)

    Brines, R.D.; Sia, D.Y.; Lehner, T.

    1987-01-01

    The authors isolated a T8 + T3 + Ia + clone of cells from the peripheral blood mononuclear cells of a healthy subject. The clone was expanded and maintained with autologous feed cells, interleukin 2, and a streptococcal antigen. The T8 + clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells,and released a soluble factor. Both the cloned cells and the corresponding soluble factor expressed augmenting helper but not suppressor activity. The augmenting helper activity for B cell antibody synthesis was demonstrable only in the presence of autologous T 4 cells. Radioimmunoassay was used to measure antibodies. Although stimulation of the T8 + cloned cells was antigen-specific, the resulting soluble factor elicited nonspecific antibody synthesis in the presence of T4 and B cells. The T8 + cloned cell-derived factor was adsorbed by B cells but not by T4 cells. Preliminary studies suggest that the factor has the properties of a B cell growth factor. They suggest that the T8 + population consists of functionally heterogeneous cell subsets, some that have suppressor function and others that augment the T4 + helper-inducer activity in B cell antibody synthesis

  17. (4,0) supersymmetric sigma-model and t-duality

    International Nuclear Information System (INIS)

    Lhallabi, T.

    1997-08-01

    The conserved supercurrents J ++ and J -- are deduced for the (4,0) supersymmetric sigma model on harmonic superspace with arbitrary background gauge connection. These are introduced in the Lagrangian density of the model by their couplings to the analytic gauge superfields Γ -- and Γ ++ . The T-duality transformations are obtained by integrating out the analytic gauge superfields. Finally the (4,0) supersymmetric anomaly is derived. (author). 20 refs

  18. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity

    International Nuclear Information System (INIS)

    Golding, H.; Munitz, T.I.; Singer, A.

    1985-01-01

    The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. The authors found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, the authors utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus

  19. Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

    Science.gov (United States)

    Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

    2018-06-01

    Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4+ T cells

    Science.gov (United States)

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Reisfeld, Brad; Zurlinden, Todd J; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Cooney, Craig A

    2016-01-01

    Aim: Autoimmune disease and CD4+ T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4+ T cells as a possible mechanism of immunotoxicity. Materials & methods: Naive and effector/memory CD4+ T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. Results: A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4+ T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. Conclusion: TCE increased epigenetic drift of specific CpG sites in CD4+ T cells. PMID:27092578

  1. Kinetic studies on binding of thyroid hormones (L-T3 and L-T4) to the receptors of lymphocyte cells isolated from uraemia subjects

    International Nuclear Information System (INIS)

    Al-Sultani, A.S.J.

    1989-01-01

    The levels of L-T 3 , L-T 4 and TSH in uremic sera have been measured by (RIA), and shown to have a decrease in both L-T 3 and L-T 4 levels with normal level of TSH for most specimens used in this study. Kinetics properties for binding of thyroid hormones L-T 3 and L-T 4 with nuclear receptors of human lymphocyte cells extracted from uremic patient have been studied and compared this result with control and hypothyroidism subjects and we obtained that uremic condition have a large effect on these nuclear receptors properties. Dissociation constant (K d ) and maximal binding capacity (MBC) of both L-T 3 and L-T 4 with these nuclear receptors have been determined, and we obtained that uremic condition did not affect on (K d ) values for both L-T 3 and L-T 4 but it affected on (MBC) values compared with normal subject. 8 tabs.; 25 figs.; 203 refs

  2. Decreased Expression of T-Cell Costimulatory Molecule CD28 on CD4 and CD8 T Cells of Mexican Patients with Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    German Bernal-Fernandez

    2010-01-01

    Full Text Available Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P<.001 and CD8 (P<.01 lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P<.05; this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P<.001. Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response.

  3. Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation

    International Nuclear Information System (INIS)

    Lee, Mi H.; Kim, Eugene; Kim, Tae S.

    2004-01-01

    4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182 780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation

  4. The exhausted CD4+CXCR5+ T cells involve the pathogenesis of human tuberculosis disease.

    Science.gov (United States)

    Bosco, Munyemana Jean; Wei, Ming; Hou, Hongyan; Yu, Jing; Lin, Qun; Luo, Ying; Sun, Ziyong; Wang, Feng

    2018-06-21

    The CD4 + CXCR5 + T cells have been previously established. However, their decreased frequency during tuberculosis (TB) disease is partially understood. The aim of this study was to explore the depletion of CD4 + CXCR5 + T cells in human TB. The frequency and function of CD4 + CXCR5 + T cells were evaluated in active TB (ATB) patients and healthy control (HC) individuals. The function of CD4 + CXCR5 + T cells was determined after blockade of inhibitory receptors. The frequency of CD4 + CXCR5 + T cells was decreased in ATB patients. The expression of activation markers (HLA-DR and ICOS) and inhibitory receptors (Tim-3 and PD-1) on CD4 + CXCR5 + T cells was increased in ATB group. TB-specific antigen stimulation induced higher expression of inhibitory receptors than phytohemagglutinin stimulation in ATB group. In contrast, TB antigen stimulation did not induce a significantly increased expression of IL-21 and Ki-67 on CD4 + CXCR5 + T cells. However, blockade of inhibitory receptors Tim-3 and PD-1 not only increased the frequency of CD4 + CXCR5 + T cells, but also restored their proliferation and cytokine secretion potential. An increased expression of inhibitory receptors involves the depletion of CD4 + CXCR5 + T cells, and blockade of inhibitory receptors can restore the function of CD4 + CXCR5 + T cells in ATB patients. Copyright © 2018. Published by Elsevier Ltd.

  5. Nueva Área Terminal (NAT del aeropuerto de Madrid-Barajas T-4

    Directory of Open Access Journals (Sweden)

    Lamela, A.

    2006-03-01

    Full Text Available This paper deals with the New Terminal Area of the Barajas airport. Its first part indicates the participants in the design and construction, as well as some general data. In the second part, organised like a data chart, technical data, such as general information, construction aspects, parking area, data about the building itself and others, are expressed in a concise way. The third part analyzes the construction aspects of the NAT Building, related to the power efficiency. The paper ends with a note that the author of the project has considered of interest about the functionality of the T4. Drawings, details and photographs that show the work in their total magnitude are also included.El articulo que se presenta trata de la Nueva Área Terminal (NAT del aeropuerto de Barajas y está diferenciado en una primera parte, donde se indican los créditos del proyecto y de la construcción, así como algunos datos generales. En el punto 2 y organizado como ficha, aparecen de forma escueta los datos técnicos, tales como: información general, sobre la construcción, sobre los aparcamientos, sobre el edificio terminal y otras. En el punto 3 se analizan los aspectos de la edificación NAT, relacionados con la eficiencia energética y finaliza el artículo con una nota sobre la funcionalidad de la T4, que el autor del proyecto ha considerado de interés. Se incluyen planos detalles y fotografías que muestran la obra en su total magnitud.

  6. Role of Gag and lipids during HIV-1 assembly in CD4 T cells and Macrophages

    Directory of Open Access Journals (Sweden)

    Charlotte eMariani

    2014-06-01

    Full Text Available HIV-1 is an RNA enveloped virus that preferentiallyinfects CD4+ T lymphocytes andalso macrophages. In CD4+ T cells, HIV-1mainly buds from the host cell plasma membrane.The viral Gag polyprotein targets theplasma membrane and is the orchestrator ofthe HIV assembly as its expression is sufficientto promote the formation of virus-likeparticles particles carrying a lipidic envelopederiving from the host cell membrane. Certainlipids are enriched in the viral membraneand are thought to play a key role in theassembly process and the envelop composition.A large body of work performed oninfected CD4+ T cells has provided importantknowledge about the assembly process andthe membrane virus lipid composition. WhileHIV assembly and budding in macrophages isthought to follow the same general Gag-drivenmechanism as in T-lymphocytes, the HIV cyclein macrophage exhibits specific features.In these cells, new virions bud from the limitingmembrane of seemingly intracellular compartments,where they accumulate while remaininginfectious. These structures are now oftenreferred to as Virus Containing Compartments(VCCs. Recent studies suggest that VCCsrepresent intracellularly sequestered regionsof the plasma membrane, but their precisenature remains elusive. The proteomic andlipidomic characterization of virions producedby T cells or macrophages has highlightedthe similarity between their composition andthat of the plasma membrane of producercells, as well as their enrichment in acidiclipids, some components of raft lipids andin tetraspanin-enriched microdomains. Greatchances are that Gag promotes the coalescenceof these components into an assemblyplatform from which viral budding takesplace. How Gag exactly interacts with membranelipids and what are the mechanisms involvedin the interaction between the differentmembrane nanodomains within the assemblyplatform remains unclear. Here we review recentliterature regarding the role of Gag andlipids

  7. Influence of carbamazepin and diclofenac on the radio-T3/T4-distribution and the maximal binding capacity of thyroid hormone binding proteins

    International Nuclear Information System (INIS)

    Sternad, H.; Albrecher, B.; Langsteger, W.; Eber, O.

    1993-01-01

    Marked changes in plasma thyroid function parameters due to medication have been described in literature. We, therefore, studied the influence of routine administration of carbamazepine and diclofenac upon the radio T3/T4 distribution to specific thyroid transport proteins as well as their maximal binding capacity (MBC) for T4. Both drugs have been found to lead to changes in T3 and T4 distribution but not to any influence upon MBC. The parameters of thyroid function mostly revealed reduced FT3 and FT4 values while bTSH was affected only by carbamazepine administration. (authors)

  8. HIV-specific cytotoxic T lymphocyte precursors exist in a CD28-CD8+ T cell subset and increase with loss of CD4 T cells.

    Science.gov (United States)

    Lewis, D E; Yang, L; Luo, W; Wang, X; Rodgers, J R

    1999-06-18

    To determine whether the CD28-CD8+ T cells that develop during HIV infection contain HIV-specific cytotoxic precursor cells. CD8 subpopulations from six asymptomatic HIV-positive adults, with varying degrees of CD4 T cell loss, were sorted by flow cytometry and HIV-specific precursor cytotoxic T lymphocyte frequencies were measured. Three populations of CD8 T cells were tested: CD28+CD5-- T cells, CD28-CD57+ T cells (thought to be memory cells) and CD28-CD57- T cells (function unknown). Sorted CD8 subsets were stimulated with antigen presenting cells expressing HIV-1 Gag/Pol molecules. Cytotoxic T cell assays on Gag/Pol expressing 51Cr-labeled Epstein-Barr virus transformed autologous B cells lines or control targets were performed after 2 weeks. Specific lysis and precursor frequencies were calculated. Both CD28 positive and CD28-CD57+ populations contained appreciable numbers of precursors (9-1720 per 10(6) CD8+ T cells). However, the CD28-CD57- population had fewer precursors in five out of six people studied. More CD28 positive HIV-specific cytotoxic T lymphocyte precursors were found in patients with CD4:CD8 ratios > 1, whereas more CD28-CD57+ precursors were found in patients whose CD4:CD8 ratios were < 1 (r2, 0.68). Memory HIV-specific precursor cytotoxic T lymphocytes are found in both CD28 positive and CD28-CD8+ cells, however, a CD28-CD57- subpopulation had fewer. Because CD28-CD57+ cells are antigen-driven with limited diversity, the loss of CD28 on CD8 T cells during disease progression may reduce the response to new HIV mutations; this requires further testing.

  9. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)

    2016-10-15

    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  10. Quorum sensing in CD4+ T cell homeostasis: a hypothesis and a model.

    Directory of Open Access Journals (Sweden)

    Afonso R.M. Almeida

    2012-05-01

    Full Text Available Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to count the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.

  11. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Laurence Madera

    Full Text Available Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression.

  12. Results of surgical treatment of T4 non-small cell lung cancer

    NARCIS (Netherlands)

    Pitz, CCM; de la Riviere, AB; van Swieten, HA; Westermann, CJJ; Lammers, JWJ; van den Bosch, JMM

    2003-01-01

    Objective: Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with

  13. Involvement of IRF4 dependent dendritic cells in T cell dependent colitis

    DEFF Research Database (Denmark)

    Pool, Lieneke; Rivollier, Aymeric Marie Christian; Agace, William Winston

    in genetically susceptible individuals and pathogenic CD4+ T cells, which accumulate in the inflamed mucosa, are believed to be key drivers of the disease. While dendritic cells (DCs) are important in the priming of intestinal adaptive immunity and tolerance their role in the initiation and perpetuation...... of chronic intestinal inflammation remains unclear. In the current study we used the CD45RBhi T cell transfer model of colitis to determine the role of IRF4 dependent DCs in intestinal inflammation. In this model naïve CD4+ T cells when transferred into RAG-/- mice, proliferate and expand in response...... to bacterial derived luminal antigen, localize to the intestinal mucosa and induce colitis. Adoptive transfer of naïve T cells into CD11cCre.IRF4fl/fl.RAG-1-/- mice resulted in reduced monocyte recruitment to the intestine and mesenteric lymph nodes (MLN) compared to Cre- controls. Inflammatory cytokines...

  14. Participation of L3T4 in T cell activation in the absence of class II major histocompatibility complex antigens. Inhibition by anti-L3T4 antibodies is a function both of epitope density and mode of presentation of anti-receptor antibody

    DEFF Research Database (Denmark)

    Owens, T; Fazekas de St Groth, B

    1987-01-01

    two monoclonal antibodies, KJ16-133.18 and F23.1, that recognize a determinant encoded by the T cell receptor V beta 8 gene family. These antibodies were used to select two clones of T cells with surface phenotype Thy-1.2+, L3T4+, Lyt-2-, KJ16-133.18+, F23.1+, IA-, IE-. One of these clones (E9.D4......The recognition of many class II major histocompatibility complex (MHC)-associated antigens by T cells requires the participation of the L3T4 molecule. It has been proposed that this molecule acts to stabilize low affinity binding to antigen in association with MHC and thereby increases the avidity...... of T cell/antigen interactions. By using antibodies against the T cell antigen receptor (TCR) to activate T cells, thereby circumventing the requirement for antigen presenting cells and MHC-associated antigen, we have been able to study the function of L3T4 in the absence of class II MHC. We have used...

  15. Focused genetic recombination of bacteriophage t4 initiated by double-strand breaks.

    Science.gov (United States)

    Shcherbakov, Victor; Granovsky, Igor; Plugina, Lidiya; Shcherbakova, Tamara; Sizova, Svetlana; Pyatkov, Konstantin; Shlyapnikov, Michael; Shubina, Olga

    2002-10-01

    A model system for studying double-strand-break (DSB)-induced genetic recombination in vivo based on the ets1 segCDelta strain of bacteriophage T4 was developed. The ets1, a 66-bp DNA fragment of phage T2L containing the cleavage site for the T4 SegC site-specific endonuclease, was inserted into the proximal part of the T4 rIIB gene. Under segC(+) conditions, the ets1 behaves as a recombination hotspot. Crosses of the ets1 against rII markers located to the left and to the right of ets1 gave similar results, thus demonstrating the equal and symmetrical initiation of recombination by either part of the broken chromosome. Frequency/distance relationships were studied in a series of two- and three-factor crosses with other rIIB and rIIA mutants (all segC(+)) separated from ets1 by 12-2100 bp. The observed relationships were readily interpretable in terms of the modified splice/patch coupling model. The advantages of this localized or focused recombination over that distributed along the chromosome, as a model for studying the recombination-replication pathway in T4 in vivo, are discussed.

  16. The role of CD4 in antigen-independent activation of isolated single T lymphocytes

    DEFF Research Database (Denmark)

    Kelso, A; Owens, T

    1988-01-01

    The membrane molecule CD4 (L3T4) is thought to facilitate activation of Class II H-2-restricted T cells by binding to Ia determinants on antigen-presenting cells. Recent reports suggest that CD4 can also contribute to antigen-independent activation by anti-T cell receptor (TCR) antibodies. An ass...

  17. Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

    Science.gov (United States)

    Verhoeven, D; Sankaran, S; Dandekar, S

    2007-08-01

    Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

  18. HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor immunity.

    Science.gov (United States)

    Meng, Fanzhi; Zhen, Shoumei; Song, Bin

    2017-08-01

    In East Asia and sub-Saharan Africa, chronic infection is the main cause of the development of hepatocellular carcinoma, an aggressive cancer with low survival rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy. Here, we investigated the possibility of using HBV-specific CD4 + cytotoxic T cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic CD4 + and CD8 + T cells were identified by HBV peptide pool stimulation. We found that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic CD4 + T cells and cytotoxic CD8 + T cells were present at similar numbers. But compared to the CD8 + cytotoxic T cells, the CD4 + cytotoxic T cells secreted less cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less effective at eliminating tumor cells. In addition, despite being able to secrete cytolytic factors, CD4 + T cells suppressed the cytotoxicity mediated by CD8 + T cells, even when CD4 + CD25 + regulator T cells were absent. Interestingly, we found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the cytotoxic CD4 + T cells. Neutralization of IL-10 abrogated the suppression of CD8 + T cells by CD4 + CD25 - T cells. Neither the frequency nor the absolute number of HBV-specific CD4 + cytotoxic T cells were correlated with the clinical outcome of advanced stage hepatocellular carcinoma patients. Together, this study demonstrated that in HBV-related hepatocellular carcinoma, CD4 + T cell-mediated cytotoxicity was present naturally in the host and had the potential to exert antitumor immunity, but its capacity was limited and was associated with immunoregulatory properties. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  19. Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection.

    Directory of Open Access Journals (Sweden)

    Joseph P Casazza

    2009-10-01

    Full Text Available Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1alpha and MIP-1beta mRNA, resulting in a rapid increase in production of MIP-1alpha and MIP-1beta after cognate antigen stimulation. Production of beta-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of beta-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1beta contained 10 times less Gag DNA than did those which failed to produce MIP-1beta. These data suggest that CD4+ T cells which produce MIP-1alpha and MIP-1beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.

  20. T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity

    Directory of Open Access Journals (Sweden)

    Verhoef Adrienne

    2005-01-01

    Full Text Available Background Synthetic peptides, representing CD4+ T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. Methods and Findings In this study we address the mechanism of action of peptide immunotherapy (PIT in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4+ cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4neg PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4+ and CD8+ PBMCs. Conclusion This study provides evidence for the induction of a population of CD4+ T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.

  1. Observation on the stability of the solid phase microparticles separating technique in T3, T4 radioimmunoassay

    International Nuclear Information System (INIS)

    Chen Guangliang; Chen Xunmin

    1995-01-01

    The solid phase T 3 ,T 4 RIA is adopted at various laboratories. The data analysis from the effective dose and quality control of samples indicates that the separation technique is of good effect and high stability. It is an effective separation technique for the quality control in RIA

  2. Subjective perception of safety in healthy individuals working with 7 T MRI scanners: a retrospective multicenter survey.

    Science.gov (United States)

    Fatahi, Mahsa; Demenescu, Liliana Ramona; Speck, Oliver

    2016-06-01

    To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. A total of 66 healthy individuals with a mean age of 31 ± 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the number of hours per week spent in the vicinity of the 7 T MRI scanner or the duration of experience with 7 T MRI. More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI scanners. However, participants' perceptions of safety were not affected by the prevalence of MR-related symptoms. The overall data indicated an average perception of a moderately safe work environment. To our knowledge, this study delineates the first attempt to assess the subjective safety perception among 7 T MRI workers and suggests further investigations are indicated.

  3. Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4+ T cells

    Science.gov (United States)

    Li, Peilin; Fujimoto, Katsuya; Bourguingnon, Lilly; Yukl, Steven; Deeks, Steven; Wong, Joseph K

    2014-01-01

    Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4+ T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4+ T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4+ T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4+ T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4+ T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection. PMID:24957217

  4. 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.

    Directory of Open Access Journals (Sweden)

    Hampartsoum B Barsoumian

    Full Text Available Costimulation with the recombinant SA-4-1BBL agonist of 4-1BB receptor on conventional CD4+ T cells (Tconvs overcomes the suppression mediated by naturally occurring CD4+CD25+FoxP3+ T regulatory cells (Tregs. The mechanistic basis of this observation has remained largely unknown. Herein we show that Tconvs, but not Tregs, are the direct target of SA-4-1BBL-mediated evasion of Treg suppression. IL-2 produced by Tconvs in response to 4-1BB signaling is both necessary and sufficient for overcoming Treg suppression. Supernatant from Tconvs stimulated with SA-4-1BBL contains high levels of IL-2 and overcomes Treg suppression in ex vivo Tconv:Treg cocultures. Removal of IL-2 from such supernatant restores Treg suppression and repletion of Tconv:Treg cocultures with exogenous recombinant IL-2 overcomes suppression. This study establishes 4-1BB signaling as a key circuit that regulates physical and functional equilibrium between Tregs and Tconvs with important implications for immunotherapy for indications where a fine balance between Tregs and Teffs plays a decisive role.

  5. The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia

    DEFF Research Database (Denmark)

    Gay, D; Buus, S; Pasternak, J

    1988-01-01

    The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell...... proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T...... cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target....

  6. Transcriptomic analysis of mouse EL4 T cells upon T cell activation and in response to protein synthesis inhibition via cycloheximide treatment

    Directory of Open Access Journals (Sweden)

    Pek Siew Lim

    2016-03-01

    Full Text Available T cell activation involves the recognition of a foreign antigen complexed to the major histocompatibility complex on the antigen presenting T cell to the T cell receptor. This leads to activation of signaling pathways, which ultimately leads to induction of key cytokine genes responsible for eradication of foreign antigens. We used the mouse EL4 T cell as a model system to study genes that are induced as a result of T cell activation using phorbol myristate acetate (PMA and calcium ionomycin (I as stimuli. We were also interested to examine the importance of new protein synthesis in regulating the expression of genes involved in T cell activation. Thus we have pre-treated mouse EL4 T cells with cycloheximide, a protein synthesis inhibitor, and left the cells unstimulated or stimulated with PMA/I for 4 h. We performed microarray expression profiling of these cells to correlate the gene expression with chromatin state of T cells upon T cell activation [1]. Here, we detail further information and analysis of the microarray data, which shows that T cell activation leads to differential expression of genes and inducible genes can be further classified as primary and secondary response genes based on their protein synthesis dependency. The data is available in the Gene Expression Omnibus under accession number GSE13278. Keywords: EL4 T cell, Microarray, T cell activation, Inducible genes

  7. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

    Science.gov (United States)

    McNally, Alice; Hill, Geoffrey R.; Sparwasser, Tim; Thomas, Ranjeny; Steptoe, Raymond J.

    2011-01-01

    CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion. PMID:21502514

  8. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  9. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease.

    Science.gov (United States)

    Mattoo, Hamid; Mahajan, Vinay S; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S; Kulikova, Maria; Drijvers, Jefte M; Daccache, Joe; Carruthers, Mollie N; Castelino, Flavia V; Stone, James R; Stone, John H; Pillai, Shiv

    2016-09-01

    IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG4-RD lesions. We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD based on their clonal expansion and ability to infiltrate affected tissue sites. We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG4-RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4(+)SLAMF7(+) cytotoxic T lymphocytes (CTLs) and CD4(+)GATA3(+) TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. CD4(+) effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4(+) CTLs but not CD4(+)GATA3(+) memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally expanded CD4(+) CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4(+) CTLs. IgG4-RD is prominently linked to clonally expanded IL-1β- and TGF-β1-secreting CD4(+) CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4(+) T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection

    Directory of Open Access Journals (Sweden)

    Deborah M. Brown

    2016-03-01

    Full Text Available CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL play a role in chronic, as well as, acute infections such as influenza A virus (IAV infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections such as HIV, mouse pox, murine gamma herpes virus, CMV, EBV and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and anti-tumor immunity through their ability to acquire perforin mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other anti-viral and anti-tumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell mediated immune protection against heterosubtypic IAV infection.

  11. Sensitive radioimmunoassay of total thyroxine (T4) in horses using a simple extraction method.

    Science.gov (United States)

    Tangyuenyong, Siriwan; Nambo, Yasuo; Nagaoka, Kentaro; Tanaka, Tomomi; Watanabe, Gen

    2017-07-28

    Most thyroid hormone determinations in animals are based on immunoassays adapted from those used to test human samples, which may not reflect the actual values of thyroid hormone in horses because of the presence of binding proteins. The aims of the present study were i) to establish a novel radioimmunoassay (RIA) using a more simple and convenient method to separate binding proteins for the measurement of total thyroxine (T4) in horses and ii) to validate the assay by comparing total T4 concentrations in yearling horses raised in different climates. Blood samples were collected from trained yearlings in Hokkaido (temperate climate) and Miyazaki (subtropical climate) in Japan and from adult horses in estrus and diestrus. T4 was extracted from both serum and plasma using modified acid ethanol cryo-precipitation and sodium acetate ethanol methods. Circulating total T4 concentrations were determined by RIA. T4 concentration by sodium acetate ethanol was appropriately detectable rather than sodium salicylate method and was the same as for acid ethanol method. Furthermore, this sodium acetate ethanol method required fewer extraction steps than the other methods. Circulating T4 concentrations in yearlings were 225.98 ± 20.89 ng/ml, which was higher than the previous reference values. With respect to climate, T4 levels in Hokkaido yearlings tended to be higher than those in Miyazaki yearlings throughout the study period. These results indicated that this RIA protocol using a modified sodium acetate ethanol separation technique might be an appropriate tool for specific measurement of total T4 in horses.

  12. IT3T/3 - Working remotely with Windows XP

    CERN Multimedia

    CERN. Geneva; Vitè, Davide F; Wagner, Andreas

    2005-01-01

    CERN Technical Training 2005: IT3T - IT Technical Training Tutorials (Summer 2005) The presentation will explain how to configure and use your Windows computer when abroad from CERN, either at home or when traveling. How to access your files, the Distributed File System (DFS) space; how to read your mails; how to work remotely on CERN resources using Terminal Services are all the questions that will be addressed during this tutorial. The tutorials are free of charge, but separate registration to each is required. Participation to any of the tutorials is open: attendance to any tutorial is not a prerequisite to attend subsequent ones. If you are interested in attending, please discuss with your supervisor and/or your DTO, and apply electronically via EDH. Registered participants will be invited to each tutorial; attendance will be recorded in the personal training records. More information, online registration, and the detailed IT3T programmes are available on the IT Technical Training Tutorials webpage, http:...

  13. Increasing doses effect of L-T4 and L-T3 in the hypothalamus - hypophysis - thyroid in patients carrier of congenital and acquired hypothyroidism

    International Nuclear Information System (INIS)

    Cavaliere, H.

    1987-01-01

    The pituitary and peripheral response to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2, and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. Since all patients received similar doses of thyroid hormones (μg/Kg of body weight) and had similar serum levels of T4 and T3 on each dose of L-T4 or L-T3, this paper concludes that congenitally hypothyroid patients have persistent pituitary resistance, but no peripheral resistance, to thyroid hormone. (author)

  14. Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

    Science.gov (United States)

    Biondi, Bernadette; Wartofsky, Leonard

    2012-07-01

    Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

  15. Phage T4 endonuclease SegD that is similar to group I intron endonucleases does not initiate homing of its own gene.

    Science.gov (United States)

    Sokolov, Andrey S; Latypov, Oleg R; Kolosov, Peter M; Shlyapnikov, Michael G; Bezlepkina, Tamara A; Kholod, Natalia S; Kadyrov, Farid A; Granovsky, Igor E

    2018-02-01

    Homing endonucleases are a group of site-specific endonucleases that initiate homing, a nonreciprocal transfer of its own gene into a new allele lacking this gene. This work describes a novel phage T4 endonuclease, SegD, which is homologous to the GIY-YIG family of homing endonucleases. Like other T4 homing endonucleases SegD recognizes an extended, 16bp long, site, cleaves it asymmetrically to form 3'-protruding ends and digests both unmodified DNA and modified T-even phage DNA with similar efficiencies. Surprisingly, we revealed that SegD cleavage site was identical in the genomes of segD - and segD + phages. We found that segD gene was expressed during the T4 developmental cycle. Nevertheless, endonuclease SegD was not able to initiate homing of its own gene as well as genetic recombination between phages in its site inserted into the rII locus. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Labelled T{sub 3}, T{sub 4} and TBP for In Vitro Testing of Thyroid Function in Man and Animals

    Energy Technology Data Exchange (ETDEWEB)

    Czerniak, P.; Boruchowski, Sabina; Shomron, I. [Dept. of Radiotherapy and Isotopes, Tel-Hashomer Hospital, Tel-Aviv University Medical School, Faculty of Continuing Medical Education, Tel-Aviv (Israel)

    1970-02-15

    Iodothyronines are bound to determined electrophoretic fractions of serum proteins - TBP (TBG, TBA, TBPA). Radioiodine labelled T{sub 3} and T{sub 4} complex the free TBP fractions until saturation. The excess of added in vitro thyronines is then absorbed by the RBC. The changes described can be detected and quantitatively determined by radioisotope tests: radioelectrophoresis - T{sub 3/4} BP test, and RBC - {sup 125}I T{sub 3} test (Hamolsky test). The in vitro tests of the thyroid function can be clinically reliable if the protein fractions are normal, and they may be altered without thyroid pathology if the TBG fractions are abnormal. The electrophoretic fractions vary quantitatively and qualitatively in animals of different classes and orders. We chose these features to study the correlation between iodothyronines, plasma proteins and the above-mentioned thyroid tests. Twenty-two animal species (arranged according to the increasing percentage of the Hamolsky test) were examined: goat (8.6%, cow, lamb, calf, man, camel, goose, hamster, rat, turkey, marmot, duck, horse, donkey, hen, dog, pigeon, rabbit, guinea-pig, mouse, fish and frog (91.5%). The following additional parameters were examined: PBI, serum quantitative electrophoresis, T{sub 3} BP studies. All the tests were performed under identical technical conditions. Results and conclusions: (1) The Hamolsky test in the examined animals ranges from 9% to 92%. It is highest in the poicolothermics, in which much prealbumin and few glubulins are found on electrophoresis. The T{sub 3} BP is low, and about a half of the added {sup 125}I T{sub 3} remains unbound. (2) T{sub 3} and T{sub 4} are complexed with T{sub 3} BP and T{sub 4} BP fractions, which correspond to prealbumin, albumin, alpha 1-2, beta and exceptionally gamma globulin. The fractions are variable but characteristic for each animal species. T{sub 3} BP does not correlate exactly with T{sub 4} BP, and seems to be distributed over more fractions

  17. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

    Science.gov (United States)

    Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

    2017-09-01

    Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca 2+ )-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca 2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1 -/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1 + TRPV1 + T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1 -/- CD4+ T cells have increased T-cell receptor-induced Ca 2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1 + TRPV1 + T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    OpenAIRE

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2009-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

  19. Working with Windows Vista at CERN - (IT3T/2007/3)

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    IT3T/2007/3 - Travailler sur Windows Vista au CERN La présentation fournira une introduction à Windows Vista et montrera les nouvelles fonctionnalités comme le nouveau interface d’utilisateur : Windows Aero, le nouveau Windows Desktop Search et les divers améliorations de sécurité comme User Account Control. IT3T/2007/3 - Working with Windows Vista at CERN The presentation will provide a introduction to Windows Vista and demonstrate the new features such as the new Graphical User Interface including Windows Aero, the new Windows Desktop Search and various Security enhancements like the User Account Control.

  20. CXC chemokine receptor 4 expression and stromal cell-derived factor-1alpha-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 and interleukin-10

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H

    2000-01-01

    -10. IL-4 and IL-10 up- or down-regulated CXCR4 mRNA expression in CD4+ T lymphocytes, respectively, as detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Scatchard analysis revealed a type of CXCR4 with affinity (Kd approximately 6.3 nM), and approximately 70....... The regulation of CXCR4 expression in CD4+ T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP-dependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4+ T lymphocytes via both c......AMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4+ T lymphocytes is not linked to calcium...

  1. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

    Science.gov (United States)

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-11-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS_9 and PAS_11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

  2. Lack of association between cytotoxic T-lymphocyte antigen 4 (CTLA-4 -1722T/C (rs733618 polymorphism and cancer risk: from a case-control study to a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Weifeng Tang

    Full Text Available BACKGROUND: The association between cytotoxic T-lymphocyte antigen 4 (CTLA-4 gene -1722T/C polymorphism (rs733618 and cancer has been widely assessed, and a definitive conclusion remains elusive. We first performed a hospital based case-control study to measure this association of esophageal cancer with CTLA-4 -1722T/C polymorphism in Han Chinese population, and then carried out a meta-analysis to obtain a comprehensive evaluation for this issue. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study involved 629 esophageal squamous cell carcinoma (ESCC cases and 686 age and gender well matched cancer-free controls. PCR-LDR (polymerase chain reaction-ligase detection reactions method was used to identify genotypes. Meta-analysis was conducted by STATA (v12.0 software. This case-control study showed no significant difference in the genotype and allele distributions of CTLA-4 -1722T/C polymorphism between esophageal cancer cases and control subjects, in accord with the findings of the further meta-analysis in all genetic models. Evidence of large heterogeneity was observed among all eligible studies in the recessive model. Further subgroup analyses by ethnicity, cancer type and system, detected null associations in this meta-analysis. CONCLUSION: This case-control study and the further meta-analysis, failed to identify the association between CTLA-4 -1722T/C polymorphism and cancer risk.

  3. Hormonal evaluation of T{sub 4} and T{sub 3} through radioimmunoassay in younglings of rats with hypothyroidism; Avaliacao hormonal de T{sub 4} e T{sub 3} atraves de radioimunoensaio em filhotes de ratas hipotireoideas

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, M.F.G. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Silva, I.M.S.; Pereira, S.S.L.; Souza, G.M.L.; Carvalho, E.F.M.B.; Cavalcante, C.V.G. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia; Lima Filho, G.L.; Catanho, M.T.J.A. [Faculdade de Formacao de Professores de Nazare da Mata, PE (Brazil). Dept. de Ciencias Naturais

    2000-07-01

    The onset of fetal thyroid function occurs about 17-18 days after conception in the rat. The maternal hypothyroidism which occurs during gestation provokes alteration in the rat after birth. Due to this alteration, we decided to analyze the hormonal modification in the newborn rats. The hypothyroidism was induced in normal dams, which were being treated for 7 days with MMI (in the concentration of 0,03% in drinking water) before mating. Another dam group which was submitted to an induction of hypothyroidism maintained the treatment with MMI for 13 days during gestation. The hormones were assessed by radioimmunoassay technique. It was seen that the rats which were born from hypothyroid dams suffered alterations on its T{sub 4} and T{sub 3} hormone levels concerning to 10, 30 and 60 days after birth. There was also modifications on their weight and size. The growth is affected throughout post-natal life by thyroid hormones, which has a facilitator influence on growth hormone economy, as opposed to the inhibitory effects on TSH economy. The administration of MMI bars the fetal thyroid gland function, causing a decrease of both T{sub 4} and T{sub 3} levels, even after the birth, indicating that the maternal hypothyroidism influences on the post-natal life of the rat. (author)

  4. S3T working group. Report 1: group aims

    International Nuclear Information System (INIS)

    Pouey, M.

    1983-04-01

    The work group S3T which is aimed to designing and developing devices using unconventional holographic optics is presented. These devices find applications that are classified here in four items high resolution spectrometers, high definition imaging, high flux devices, metrology and interferometry. The problems to solve and the aims of the group in each of these cases are presented. Three synthesis of lectures are in this report. The main one concerns stigmatism conditions of concave holographic gratings used in normal incidence. This new process of focusing is very interesting for hot plasma diagnostics [fr

  5. The titanium tris-anilide cation [Ti(N[(t)Bu]Ar)3](+) stabilized as its perfluoro-tetra-phenylborate salt: structural characterization and synthesis in connection with redox activity of 4,4'-bipyridine dititanium complexes.

    Science.gov (United States)

    Spinney, Heather A; Clough, Christopher R; Cummins, Christopher C

    2015-04-21

    This work explores the reduction of 4,4'-bipyridine using two equivalents of the titanium(iii) complex Ti(N[(t)Bu]Ar)3 resulting in formation of a black, crystalline complex, (4,4'-bipy){Ti(N[(t)Bu]Ar)3}2, for which an X-ray structure determination is reported. The neutral, black, 4,4'-bipyridine-bridged bimetallic was found to be redox active, with mono- and di-anions being accessible electrochemically, and with the mono- and di-cations also being accessible chemically, and isolable, at least when using the weakly coordinating anion [B(C6F5)4](-) as the counter-ion. It proved possible to crystallize the salt [(4,4'-bipy){Ti(N[(t)Bu]Ar)3}2][B(C6F5)4]2 for a single-crystal X-ray structure investigation; in this instance it was revealed that the aromaticity of the 4,4'-bipyridine ligand, that had been disrupted upon reduction, had been regained. A rare cationic d(0) metal tris-amide complex, shown by X-ray crystallography to contain an intriguing pyramidal TiN3 core geometry, namely {Ti(N[(t)Bu]Ar)3}(+), could also be isolated when using [B(C6F5)4] as the essentially non-interacting counter-ion. This highly reactive cation should be considered as a potential intermediate in the plethora of reactions wherein Ti(N[(t)Bu]Ar)3 has been shown to effect the reduction of substrates including halogenated organic molecules, carbonyl compounds, organic nitriles, and metal complexes.

  6. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

    Science.gov (United States)

    Han, Song Hee; Hur, Min Seok; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

    2017-10-01

    Previous studies have shown the expression of histamine H 4 receptor (H4R) on CD4 + T cells, especially human CD4 + T h 2-polarized T cells. This study aimed to investigate the role of H4R on these effector T cells in psoriasis. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4 + T cells. Then, we identified H4R expression in dermal CD4 + T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4 + T cells with several inflammatory cytokines. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T h 17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4 + T cells were polarized into T h 17 cells, we observed a tendency toward suppressed IL-17 secretion. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4 + T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  7. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Kara G Lassen

    2006-07-01

    Full Text Available HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART. We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications.

  8. Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Michaela Lucas

    2007-07-01

    Full Text Available CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays.Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C.During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

  9. Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

    Science.gov (United States)

    Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

    2015-05-20

    Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

  10. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.

    Science.gov (United States)

    Tokoyoda, Koji; Zehentmeier, Sandra; Hegazy, Ahmed N; Albrecht, Inka; Grün, Joachim R; Löhning, Max; Radbruch, Andreas

    2009-05-01

    CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.

  11. Mitofusin 2 Promotes Apoptosis of CD4+ T Cells by Inhibiting Autophagy in Sepsis

    Directory of Open Access Journals (Sweden)

    Lan Ying

    2017-01-01

    Full Text Available Apoptosis of CD4+ T cells is a primary pathophysiological mechanism of immune dysfunction in the pathogenesis of sepsis. Mitofusin 2 (Mfn2, an integral mitochondrial outer membrane protein, has been confirmed to be associated with cellular metabolism, proliferation, and apoptosis. The function of Mfn2 in CD4+ T cell apoptosis in sepsis is poorly understood. Here, we discovered increased in vivo Mfn2 expression, autophagy deficiency, and elevated cell apoptosis in murine splenic CD4+ T cells after cecal ligation and puncture (CLP. We also observed almost identical results in splenic CD4+ T cells upon lipopolysaccharide (LPS stimulation in vitro. Furthermore, overexpression of Mfn2 resulted in impaired autophagy and increased apoptosis in Jurkat cells. Pharmacological inhibition of autophagy with 3-methyladenine enhanced Mfn2 overexpression-induced cell apoptosis. In addition, overexpression of Mfn2 downregulated phorbol myristate acetate (PMA/ionomycin-, rapamycin- and starvation-induced autophagy in Jurkat T cells. Taken together, these data indicate a critical role of Mfn2 in CD4+ T cell apoptosis in sepsis and the underlying mechanism of autophagy deficiency.

  12. Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bingfen Yang

    Full Text Available CD244 (2B4 is a member of the signaling lymphocyte activation molecule (SLAM family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+ T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+ T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+ T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+ T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+ T cells, CD244/2B4-bright CD4(+ T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+ T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+ T cell function.

  13. English Language for Teachers (EL4T): a course for EFL teachers

    OpenAIRE

    Shrestha, Prithvi

    2013-01-01

    This paper reports on the design and implementation of EL4T in a large-scale project. EL4T is a self-study mobile technology-based ESP course designed to enhance Bangladeshi school English language teachers’ English language skills and pedagogical practices. Key implications of developing this course for ESP in EFL contexts will be presented.

  14. Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

    Science.gov (United States)

    Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

    2015-01-01

    A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

  15. T2-Weighted 4D Magnetic Resonance Imaging for Application in Magnetic Resonance–Guided Radiotherapy Treatment Planning

    Science.gov (United States)

    Freedman, Joshua N.; Collins, David J.; Bainbridge, Hannah; Rank, Christopher M.; Nill, Simeon; Kachelrieß, Marc; Oelfke, Uwe; Leach, Martin O.; Wetscherek, Andreas

    2017-01-01

    Objectives The aim of this study was to develop and verify a method to obtain good temporal resolution T2-weighted 4-dimensional (4D-T2w) magnetic resonance imaging (MRI) by using motion information from T1-weighted 4D (4D-T1w) MRI, to support treatment planning in MR-guided radiotherapy. Materials and Methods Ten patients with primary non–small cell lung cancer were scanned at 1.5 T axially with a volumetric T2-weighted turbo spin echo sequence gated to exhalation and a volumetric T1-weighted stack-of-stars spoiled gradient echo sequence with golden angle spacing acquired in free breathing. From the latter, 20 respiratory phases were reconstructed using the recently developed 4D joint MoCo-HDTV algorithm based on the self-gating signal obtained from the k-space center. Motion vector fields describing the respiratory cycle were obtained by deformable image registration between the respiratory phases and projected onto the T2-weighted image volume. The resulting 4D-T2w volumes were verified against the 4D-T1w volumes: an edge-detection method was used to measure the diaphragm positions; the locations of anatomical landmarks delineated by a radiation oncologist were compared and normalized mutual information was calculated to evaluate volumetric image similarity. Results High-resolution 4D-T2w MRI was obtained. Respiratory motion was preserved on calculated 4D-T2w MRI, with median diaphragm positions being consistent with less than 6.6 mm (2 voxels) for all patients and less than 3.3 mm (1 voxel) for 9 of 10 patients. Geometrical positions were coherent between 4D-T1w and 4D-T2w MRI as Euclidean distances between all corresponding anatomical landmarks agreed to within 7.6 mm (Euclidean distance of 2 voxels) and were below 3.8 mm (Euclidean distance of 1 voxel) for 355 of 470 pairs of anatomical landmarks. Volumetric image similarity was commensurate between 4D-T1w and 4D-T2w MRI, as mean percentage differences in normalized mutual information (calculated over all

  16. T2-Weighted 4D Magnetic Resonance Imaging for Application in Magnetic Resonance-Guided Radiotherapy Treatment Planning.

    Science.gov (United States)

    Freedman, Joshua N; Collins, David J; Bainbridge, Hannah; Rank, Christopher M; Nill, Simeon; Kachelrieß, Marc; Oelfke, Uwe; Leach, Martin O; Wetscherek, Andreas

    2017-10-01

    The aim of this study was to develop and verify a method to obtain good temporal resolution T2-weighted 4-dimensional (4D-T2w) magnetic resonance imaging (MRI) by using motion information from T1-weighted 4D (4D-T1w) MRI, to support treatment planning in MR-guided radiotherapy. Ten patients with primary non-small cell lung cancer were scanned at 1.5 T axially with a volumetric T2-weighted turbo spin echo sequence gated to exhalation and a volumetric T1-weighted stack-of-stars spoiled gradient echo sequence with golden angle spacing acquired in free breathing. From the latter, 20 respiratory phases were reconstructed using the recently developed 4D joint MoCo-HDTV algorithm based on the self-gating signal obtained from the k-space center. Motion vector fields describing the respiratory cycle were obtained by deformable image registration between the respiratory phases and projected onto the T2-weighted image volume. The resulting 4D-T2w volumes were verified against the 4D-T1w volumes: an edge-detection method was used to measure the diaphragm positions; the locations of anatomical landmarks delineated by a radiation oncologist were compared and normalized mutual information was calculated to evaluate volumetric image similarity. High-resolution 4D-T2w MRI was obtained. Respiratory motion was preserved on calculated 4D-T2w MRI, with median diaphragm positions being consistent with less than 6.6 mm (2 voxels) for all patients and less than 3.3 mm (1 voxel) for 9 of 10 patients. Geometrical positions were coherent between 4D-T1w and 4D-T2w MRI as Euclidean distances between all corresponding anatomical landmarks agreed to within 7.6 mm (Euclidean distance of 2 voxels) and were below 3.8 mm (Euclidean distance of 1 voxel) for 355 of 470 pairs of anatomical landmarks. Volumetric image similarity was commensurate between 4D-T1w and 4D-T2w MRI, as mean percentage differences in normalized mutual information (calculated over all respiratory phases and patients), between

  17. Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131

    Energy Technology Data Exchange (ETDEWEB)

    Rosario, Pedro Weslley Souza [Clinica de Endocrinologia e Metabologia (CEPCEM), Belo Horizonte, MG (Brazil). Centro de Estudos e Pesquisa]. E-mail: pedrorosario@globo.com; Borges, Michelle A.R.; Costa, Graciela B.C.; Resende, Leonardo L.; Padrao, Eduardo L.; Barroso, Alvaro L.; Purish, Saulo [Santa Casa de Belo Horizonte, MG (Brazil). Dept. de Tireoide. Servico de Endocrinologia; Santa Casa de Belo Horizonte, MG (Brazil). Servico de Medicina Nuclear

    2007-01-15

    Objective: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of {sup 131}I. Patients and methods: Initially, 234 low-risk patients [tumor {<=} 5 cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with {sup 131}I (3.7-5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1 ng/ml) during the first year after initial therapy were selected. Results: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new {sup 131}I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. Conclusions: All patients with Tg on T4 > 5 ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of {sup 131}I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4 {<=} 5 ng/ml and negative US and CT, only 12% presented ectopic uptake on RxWBS. These cases could be followed up by monitoring Tg on T4, and RxWBS and FDG-PET should only be performed if this marker does not decrease after 1-2 years. (author)

  18. Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131

    International Nuclear Information System (INIS)

    Rosario, Pedro Weslley Souza; Borges, Michelle A.R.; Costa, Graciela B.C.; Resende, Leonardo L.; Padrao, Eduardo L.; Barroso, Alvaro L.; Purish, Saulo; Santa Casa de Belo Horizonte, MG

    2007-01-01

    Objective: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of 131 I. Patients and methods: Initially, 234 low-risk patients [tumor ≤ 5 cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with 131 I (3.7-5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1 ng/ml) during the first year after initial therapy were selected. Results: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new 131 I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. Conclusions: All patients with Tg on T4 > 5 ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of 131 I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4 ≤ 5 ng/ml and negative US and CT, only 12% presented ectopic uptake on RxWBS. These cases could be followed up by monitoring Tg on T4, and RxWBS and FDG-PET should only be performed if this marker does not decrease after 1-2 years. (author)

  19. Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

    Directory of Open Access Journals (Sweden)

    Weihong Zeng

    2017-06-01

    Full Text Available Decidual CD4+ T (dCD4 T cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

  20. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

    Directory of Open Access Journals (Sweden)

    Maria Sophia Mackroth

    2016-11-01

    Full Text Available In acute Plasmodium falciparum (P. falciparum malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

  1. Profiling calcium signals of in vitro polarized human effector CD4+ T cells.

    Science.gov (United States)

    Kircher, Sarah; Merino-Wong, Maylin; Niemeyer, Barbara A; Alansary, Dalia

    2018-06-01

    Differentiation of naïve CD4 + T cells into effector subtypes with distinct cytokine profiles and physiological roles is a tightly regulated process, the imbalance of which can lead to an inadequate immune response or autoimmune disease. The crucial role of Ca 2+ signals, mainly mediated by the store operated Ca 2+ entry (SOCE) in shaping the immune response is well described. However, it is unclear if human effector CD4 + T cell subsets show differential Ca 2+ signatures in response to different stimulation methods. Herein, we provide optimized in vitro culture conditions for polarization of human CD4 + effector T cells and characterize their SOCE following both pharmacological store depletion and direct T-cell receptor (TCR) activation. Moreover, we measured whole cell Ca 2+ release activated Ca 2+ currents (I CRAC ) and investigated whether the observed differences correlate to the expression of CRAC genes. Our results show that Ca 2+ profiles of helper CD4 + Th1, Th2 and Th17 are distinct and in part shaped by the intensity of stimulation. Regulatory T cells (Treg) are unique being the subtype with the most prominent SOCE response. Analysis of in vivo differentiated Treg unraveled the role of differential expression of ORAI2 in fine-tuning signals in Treg vs. conventional CD4 + T cells. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  2. NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1 x T4 and Watson-Crick T1 x A4 base pairs flanking the bisintercalation site

    International Nuclear Information System (INIS)

    Gao, X.; Patel, D.J.

    1988-01-01

    The authors report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-Tr) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets records in H 2 O and D 2 O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding the dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A large set of intermolecular contacts established from nuclear Overhauser effects (NOEs) between antibiotic and nucleic acid protons in the echinomycin-tetranucleotide complexes in solution are consistent with corresponding contacts reported for echinomycin-oligonucleotide complexes in the crystalline state. The authors demonstrate that the G x G base pairs adopt Watson-Crick pairing in both d(ACGT) and d(TCGA) complexes in solution. By contrast, the A1 x T4 base pairs adopt Hoogsteen pairing for the echinomycin-d(A1-C2-G3-Tr) complex while the T1 x A4 base pairs adopt Watson-Crick pairing for the echinomycin-d(T1-C2-G3-A4) complex in aqueous solution. These results emphasize the role of sequence in discriminating between Watson-Crick and Hoogsteen pairs at base pairs flanking the echinomycin bisintercalation site in solution

  3. Achievement report for fiscal 1981 on Sunshine Part 2. Program-assisted project. Research and development of coal liquefaction technology (Development of direct coal hydroliquefaction plant; development of 2.4T/day-capable research plant); 1981 nendo sekitan ekika gijutsu no kenkyu kaihatsu / chokusetsu suiten ekika plant no kaihatsu seika hokokusho. 2. 2.4t/nichi jikken plant no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1982-03-01

    For the goal of developing a direct coal hydroliquefaction plant, designing of a 2.4T/day-capable research plant is conducted as in the preceding fiscal year, devices are purchased and manufactured, and construction work is carried out. The construction work is now over, and the plant is subjected to various inspections by the relevant Government offices. Preparatory tasks are discharged for the study of operation. The material of the 2.4T/day-capable research plant presented here is a compilation of charts of the piping routes, charts of civil engineering and construction, charts of instrumentation, charts of electrical systems, documents of approvals and licenses, etc. (NEDO)

  4. Dynamic transcription of long non-coding RNA genes during CD4+ T cell development and activation.

    Directory of Open Access Journals (Sweden)

    Fei Xia

    Full Text Available BACKGROUND: Recent evidence shows that long non-coding RNA (LncRNA play important regulatory roles in many biology process, including cell development, activation and oncogenesis. However, the roles of these LncRNAs in the development and activation of CD4+ T cells, which is an important component of immune response, remain unknown. RESULTS: To predict the function of LncRNA in the development and activation of CD4+ T cells, first, we examined the expression profiles of LncRNAs and mRNAs in CD4-CD8- (DN, CD4+CD8+ (DP, CD4+CD8-, and activated CD4+CD8- T cells in a microarray analysis and verified these results by real time PCRs (qPCR. We found that the expression of hundreds of LncRNAs significantly changed in each process of developmental transition, including DN into DP, DP into CD4+CD8-, and CD4+CD8- into activated CD4+ T cells. A Kendall distance analysis suggested that the expression of LncRNAs in DN, DP, CD4+CD8- T cells and activated CD4+ T cells were correlated with the expression of mRNAs in these T cells. The Blat algorithm and GO analysis suggested that LncRNAs may exert important roles in the development and activation of CD4+ T cells. These roles included proliferation, homeostasis, maturation, activation, migration, apoptosis and calcium ion transportation. CONCLUSION: The present study found that the expression profiles of LncRNAs in different stages of CD4+ T cells are distinguishable. LncRNAs are involved in the key biological process in CD4+ T cell development and activation.

  5. Hormonal evaluation of T4 and T3 through radioimmunoassay in younglings of rats with hypothyroidism

    International Nuclear Information System (INIS)

    Silveira, M.F.G.; Silva, I.M.S.; Pereira, S.S.L.; Souza, G.M.L.; Carvalho, E.F.M.B.; Cavalcante, C.V.G.; Lima Filho, G.L.; Catanho, M.T.J.A.

    2000-01-01

    The onset of fetal thyroid function occurs about 17-18 days after conception in the rat. The maternal hypothyroidism which occurs during gestation provokes alteration in the rat after birth. Due to this alteration, we decided to analyze the hormonal modification in the newborn rats. The hypothyroidism was induced in normal dams, which were being treated for 7 days with MMI (in the concentration of 0,03% in drinking water) before mating. Another dam group which was submitted to an induction of hypothyroidism maintained the treatment with MMI for 13 days during gestation. The hormones were assessed by radioimmunoassay technique. It was seen that the rats which were born from hypothyroid dams suffered alterations on its T 4 and T 3 hormone levels concerning to 10, 30 and 60 days after birth. There was also modifications on their weight and size. The growth is affected throughout post-natal life by thyroid hormones, which has a facilitator influence on growth hormone economy, as opposed to the inhibitory effects on TSH economy. The administration of MMI bars the fetal thyroid gland function, causing a decrease of both T 4 and T 3 levels, even after the birth, indicating that the maternal hypothyroidism influences on the post-natal life of the rat. (author)

  6. Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

    International Nuclear Information System (INIS)

    Chapman, Timothy J.; Castrucci, Maria R.; Padrick, Ryan C.; Bradley, Linda M.; Topham, David J.

    2005-01-01

    To track epitope-specific CD4 + T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA 323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA II , replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4 + T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4 + T cells were recruited to the infected lung both in the presence and absence of the OVA 323-339 epitope. These data show that, when primed, CD4 + T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection

  7. Anti-ATLA (antibody to adult T-cell leukemia virus-associated antigen), highly positive in OKT4-positive mature T-cell malignancies.

    Science.gov (United States)

    Tobinai, K; Nagai, M; Setoya, T; Shibata, T; Minato, K; Shimoyama, M

    1983-01-01

    Serum or plasma specimens from 252 patients with lymphoid malignancies were screened for reactivity with adult T-cell leukemia virus-associated antigen (ATLA), and the relationship between the immunologic phenotype of the tumor cells and ATLA reactivity was determined. Anti-ATLA antibodies were found in 24 (29.3%) of 82 patients with T-cell malignancy. In contrast, the antibodies were found in none of the 106 patients with B-cell malignancy and only rarely in patients with other lymphoid malignancies without blood transfusions. Among the patients with T-cell malignancy, anti-ATLA antibodies were found in 23 (45.1%) of the 51 patients with OKT4-positive mature T-cell (inducer/helper T-cell) malignancy, but in none of the patients with T-cell malignancy of pre-T, thymic T-cell or OKT8-positive mature T-cell (suppressor/cytotoxic T-cell) phenotype. Furthermore, among the OKT4-positive mature T-cell malignancies, the antibodies were found in 16 (84.2%) of 19 patients with ATL and in 5 (27.8%) of 18 patients with mature (peripheral) T-cell lymphoma, in none of four with typical T-chronic lymphocytic leukemia, in one of nine with mycosis fungoides and in the one patient with small-cell variant of Sézary's syndrome. These results suggest that anti-ATLA positive T-cell malignancies with OKT4-positive mature T-cell phenotype must be the same disease, because it is highly possible that they have the same etiology and the same cellular origin. In the atypical cases, it seems necessary to demonstrate monoclonal integration of proviral DNA of ATLV or HTLV into the tumor cells in order to establish the final diagnosis of ATL.

  8. Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax.

    Science.gov (United States)

    Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

    2015-10-23

    The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.

    Science.gov (United States)

    Hanon, E; Hall, S; Taylor, G P; Saito, M; Davis, R; Tanaka, Y; Usuku, K; Osame, M; Weber, J N; Bangham, C R

    2000-02-15

    The role of the cellular immune response in human T-cell leukemia virus type I (HTLV-I) infection is not fully understood. A persistently activated cytotoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of infected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations paradoxically suggest that HTLV-I is transcriptionally silent in most infected cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the immunodominant target antigen recognized by virus-specific CTLs. Furthermore, we provide direct evidence that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism. Consistent with these observations, we observed a significant negative correlation between the frequency of Tax(11-19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HTLV-I. Those results are in accordance with the view that virus-specific CTLs participate in a highly efficient immune surveillance mechanism that persistently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (Blood. 2000;95:1386-1392)

  10. Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects.

    Science.gov (United States)

    Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana; Chopra, Abha; McDonnell, Wyatt J; Wanjalla, Celestine; Barnett, Louise; Gangula, Rama; Hager, Cindy; Jung, Dae K; Engelhardt, Brian G; Jagasia, Madan H; Klenerman, Paul; Phillips, Elizabeth J; Koelle, David M; Kalams, Spyros A; Mallal, Simon A

    2017-11-01

    Select CMV epitopes drive life-long CD8 + T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 + T cells specific for human CMV (HCMV) are elevated in HIV + HCMV + subjects. To determine whether HCMV epitope-specific CD4 + T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 + T cells in coinfected HLA-DR7 + long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 + T cells were inflated among these HIV + subjects compared with those from an HIV - HCMV + HLA-DR7 + cohort or with HLA-DR7-restricted CD4 + T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 + T cells consisted of effector memory or effector memory-RA + subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX 3 CR1, CD38, or HLA-DR but less often coexpressed CD38 + and HLA-DR + The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 + T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. A novel outer-membrane anion channel (porin) as part of a putatively two-component transport system for 4-toluenesulphonate in Comamonas testosteroni T-2

    OpenAIRE

    Mampel, Jörg; Maier, Elke; Tralau, Tewes; Ruff, Jürgen; Benz, Roland; Cook, Alasdair M.

    2004-01-01

    Inducible mineralization of TSA (4-toluenesulphonate) by Comamonas testosteroni T-2 is initiated by a secondary transport system, followed by oxygenation and oxidation by TsaMBCD to 4-sulphobenzoate under the regulation of TsaR and TsaQ. Evidence is presented for a novel, presumably two-component transport system (TsaST). It is proposed that TsaT, an outer-membrane porin, formed an anion-selective channel that works in co-operation with the putative secondary transporter, TsaS, located in the...

  12. Differential requirements of CD4(+) T-cell signals for effector cytotoxic T-lymphocyte (CTL) priming and functional memory CTL development at higher CD8(+) T-cell precursor frequency.

    Science.gov (United States)

    Umeshappa, Channakeshava S; Nanjundappa, Roopa H; Xie, Yufeng; Freywald, Andrew; Xu, Qingyong; Xiang, Jim

    2013-04-01

    Increased CD8(+) T-cell precursor frequency (PF) precludes the requirement of CD4(+) helper T (Th) cells for primary CD8(+) cytotoxic T-lymphocyte (CTL) responses. However, the key questions of whether unhelped CTLs generated at higher PF are functional effectors, and whether unhelped CTLs can differentiate into functional memory cells at higher PF are unclear. In this study, ovalbumin (OVA) -pulsed dendritic cells (DC(OVA)) derived from C57BL/6, CD40 knockout (CD40(-/-)) or CD40 ligand knockout (CD40L(-/-)) mice were used to immunize C57BL/6, Ia(b-/-), CD40(-/-) or CD40L(-/-) mice, whose PF was previously increased with transfer of 1 × 10(6) CD8(+) T cells derived from OVA-specific T-cell receptor (TCR) transgenic OTI, OTI(CD40(-/-)) or OTI(CD40L(-/-)) mice. All the immunized mice were then assessed for effector and memory CTL responses. Following DC immunization, relatively comparable CTL priming occurred without CD4(+) T-cell help and Th-provided CD40/CD40L signalling. In addition, the unhelped CTLs were functional effectors capable of inducing therapeutic immunity against established OVA-expressing tumours. In contrast, the functional memory development of CTLs was severely impaired in the absence of CD4(+) T-cell help and CD40/CD40L signalling. Finally, unhelped memory CTLs failed to protect mice against lethal tumour challenge. Taken together, these results demonstrate that CD4(+) T-cell help at higher PF, is not required for effector CTL priming, but is required for functional memory CTL development against cancer. Our data may impact the development of novel preventive and therapeutic approaches in cancer patients with compromised CD4(+) T-cell functions. © 2012 Blackwell Publishing Ltd.

  13. Cross section measurement for the 10B(n ,t 2 α ) three-body reaction at 4.0, 4.5, and 5.0 MeV. II. Experimental setup and results

    Science.gov (United States)

    Wang, Zhimin; Bai, Huaiyong; Zhang, Luyu; Jiang, Haoyu; Lu, Yi; Chen, Jinxiang; Zhang, Guohui; Gledenov, Yu. M.; Sedysheva, M. V.; Khuukhenkhuu, G.

    2017-10-01

    Cross sections of the 10B(n ,t 2 α ) three-body reaction were measured at En=4.0 , 4.5, and 5.0 MeV using a twin gridded ionization chamber and a thin-film 10B sample. The present paper is the second part of the work. A digital data-acquisition system was developed for the gridded ionization chamber based on the waveform digitizer. A thin-film 10B sample was designed and prepared. The number of 10B atoms in the sample was determined by the relative method using the thermal neutron induced 10B(nt h,α )7Li and 6Li(nt h,t )4He reactions with a 6LiF sample as the reference. The measurement of the 10B(n ,t 2 α ) reaction was performed at the 4.5 MV Van de Graaff accelerator of Peking University. In the measurement, the double-coincidence technique was used, which involves the forward-backward and the grid-anode coincidence. In the data processing, the effective event area in the forward two-dimensional spectrum and the time window in the drift-time spectrum were employed to reject the background events. Cross sections of the 10B(n ,t 2 α ) and 10B(n ,α )7Li reactions were obtained. The present results are compared with the data of existing measurements and evaluations.

  14. Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine autoimmune diabetes.

    Science.gov (United States)

    Zou, Fang; Lai, Xiaoyang; Li, Jing; Lei, Shuihong; Hu, Lei

    2017-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM. To this end, mouse studies were conducted to demonstrate that CatG impacts the activation of CD4+ T cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was investigated in NOD mice on the activation of CD4+ T cells, islet β cell function, islet inflammation and β-cell apoptosis. Furthermore, NOD mice were injected with CatG siRNA in early stage to observe the effect of CatG knockdown on the activation status of CD4+ T cells and the progression of diabetes. During the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually increased and the CD4+ T cells were gradually activated, resulting in more TH1 cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced the blood glucose level, improved the function of islet β cells and reduced the activation of CD4+ T cells. Early application of CatG siRNA improved the function of islet β cells, reduced islet inflammation and β cell apoptosis, and lowered the activation level of CD4+ T cells, thus slowing down the progression of diabetes.

  15. Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4

    NARCIS (Netherlands)

    Gascan, H.; Aversa, G. G.; Gauchat, J. F.; van Vlasselaer, P.; Roncarolo, M. G.; Yssel, H.; Kehry, M.; Spits, H.; de Vries, J. E.

    1992-01-01

    In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell

  16. Design status of the NLC beam-delivery system and possible future studies

    International Nuclear Information System (INIS)

    Zimmermann, F.; Bowden, G.; Burke, D.

    1996-10-01

    The authors outline some highlights in the present design of the beam-delivery and removal system for the Next Linear Collider (NLC), and present a long list of possible or desirable future studies. On several of the listed items work has already been started since the Snowmass workshop. Other studies could be conducted, for example, in the framework of a conceptual design report (CDR)

  17. VizieR Online Data Catalog: CoRoT observation log (N2-4.4) (CoRoT, 2009-2016)

    Science.gov (United States)

    COROT Team

    2014-03-01

    CoRoT is a space astronomy mission devoted to the study of the variability with time of stars brightness, with an extremely high accuracy (100 times better than from the ground), on very long durations (up to 150 days) and a very high duty cycle (more than 90%). The mission was led by CNES in association with four french laboratories, and 7 participating countries and agencies (Austria, Belgium, Brazil, Germany, Spain, and the ESA Science Programme). The satellite is composed of a PROTEUS platform (the 3rd in the serie), and a unique instrument: a stellar photometer. It has been launched on December 27th 2006 by a Soyuz Rocket, from Baikonour. The mission has lasted almost 6 years (the nominal 3 years duration and a 3 years extension) and has observed more than 160 000 stars. It stopped to send data suddenly on November 2nd 2012. CoRoT is performing Ultra High Precision Photomery of Stars to detect and characterise the variability of their luminosity with two main directions: - variability of the object itself: oscillations, rotation, magnetic activity - variability due to external causes as bodies in orbit around the star: planets and stars The original scientific objectives were focussed on the study of stellar pulsations (asteroseismology) to probe the internal structure of stars, and the detection of small exoplanets through their "transit in front of their host star, and the measurement of their size. This lead to introduce two modes of observations, working simultaneously: - The bright star mode dedicated to very precise seismology of a small sample of bright and closeby stars (data presented in file momentarily named "astero.dat", but should change in the near future to to "bright star.dat") - The faint star mode, observing a very large number of stars at the same time, to detect transits, which are rare events, as they imply the alignment of the star, the planet and the observer (data presented in momentarily named "exo.dat" but should change in the near

  18. Synthesis and Characterization of Chitosan-p-t-Butylcalix[4]arene acid

    Science.gov (United States)

    Handayani, D. S.; Frimadasi, W.; Kusumaningsih, T.; Pranoto

    2018-03-01

    The synthesis of chitosan-p-t-butylcalix[4]arene acid was done with DIC (N, N’-diisopropylcarbodiimide) as the coupling agent. The structural analysis of the chitosan-p-t-butylcalix[4]arene acid was conducted by spectrophotometer Fourier Transform Infra Red (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the surface area was investigated by Surface Area Analysis, the Scanning Electrone Microscope (SEM) analysed the surface morphology, and also the melting point temperature was determined. FTIR analysis on Chitosan-p-t-butylcalix[4]arene provides an overlapped absorption of -OH and -NH groups at 3438.26 cm-1. Meanwhile, a C = C aromatic bond present at 1480.43 cm-1. XRD analysis shows some broaden peaks due to the amorphous phase of the prepared material. The prepared material is a brownish yellow solid, odorless and porous. The melting point, surface area, and the average pore radius are above 300 °C, 9.42 m2 / g, and 52.5938 Å, respectively.

  19. Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts.

    Science.gov (United States)

    Mori, Masato; Hashimoto, Motomu; Matsuo, Takashi; Fujii, Takao; Furu, Moritoshi; Ito, Hiromu; Yoshitomi, Hiroyuki; Hirose, Jun; Ito, Yoshinaga; Akizuki, Shuji; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Ohmura, Koichiro; Mimori, Tsuneyo

    2017-05-01

    To determine how cell-cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4 +  T cells. Naïve CD4 +  T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4 +  T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4 +  T cells, CD161 +  or CD161 - naïve CD4 +  T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed. SF enhanced naïve CD4 +  T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4 +  T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161 +  naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1. CD4 +  T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.

  20. Human Cytomegalovirus (HCMV)-Specific CD4+ T Cells Are Polyfunctional and Can Respond to HCMV-Infected Dendritic Cells In Vitro.

    Science.gov (United States)

    Jackson, Sarah E; Sedikides, George X; Mason, Gavin M; Okecha, Georgina; Wills, Mark R

    2017-03-15

    during the host's lifetime. The dysfunction of immune cells associated with the long-term carriage of HCMV has been linked with poor responses to new pathogens and vaccines when people are older. In this study, we investigated the response of a subset of immune cells (CD4 + T cells) to HCMV proteins in healthy donors of all ages, and we demonstrate that the functionality of CD4 + T cells is maintained. We also show that CD4 + T cells produce effector functions in response to HCMV-infected cells and can prevent virus spread. Our work demonstrates that these HCMV-specific immune cells retain many important functions and help to prevent deleterious HCMV disease in healthy older people. Copyright © 2017 American Society for Microbiology.

  1. Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.

    OpenAIRE

    Kanaly, S T; Hines, S A; Palmer, G H

    1993-01-01

    Pulmonary clearance of Rhodococcus equi requires functional T lymphocytes. In this study, CD8+ T-lymphocyte-deficient transgenic mice cleared virulent R. equi from the lungs while infection in CD4+ T-lymphocyte-deficient transgenic mice persisted. Although both CD4+ and CD8+ T cells function early in pulmonary defense against R. equi, clearance is dependent on CD4+ T lymphocytes.

  2. Vitamin D Actions on CD4+ T cells in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Colleen Elizabeth Hayes

    2015-03-01

    Full Text Available This review summarizes and integrates research on vitamin D and CD4+ T lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4+ T cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4+ T lymphocytes is summarized to support the thesis that calcitriol is sunlight’s main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ Treg cell and CD4+ Tr1 cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, we highlight unanswered questions that potentially informative future research directions that may speed delivery of etiology-based strategies to reduce autoimmune disease.

  3. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Science.gov (United States)

    2010-04-01

    ... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-4T Elective carryforward of unused private activity bond limit... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects). Q-2...

  4. CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.

    Directory of Open Access Journals (Sweden)

    Young Ah Lee

    Full Text Available We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs are altered in young TS patients with the 45,X karyotype compared to age-matched controls.Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years and healthy controls (n = 16 were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (- (n = 7 and TS (+ (n = 17. Tregs sorted for CD4+ CD25bright were co-cultured with autologous CD4+ CD25- target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.Despite a lower frequency of CD4+ T cells in the TS (- and TS (+ patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively, both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively. There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+ CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+ CD25- T cells was significantly impaired in the TS (- and TS (+ patients compared to controls (P = 0.003 and P = 0.041. Meanwhile, both the TS (- and TS (+ groups had lower frequencies of naïve cells (P = 0.001 for both but higher frequencies of effector memory cells (P = 0.004 and P = 0.002 than did the healthy control group.The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.

  5. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    OpenAIRE

    Martinet , Kim ,; Bloquet , Stéphane; Bourgeois , Christine

    2014-01-01

    International audience; BackgroundCD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue ...

  6. Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells

    Science.gov (United States)

    Jensen, Helle; Folkersen, Lasse; Skov, Søren

    2012-01-01

    NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression. PMID:22870231

  7. Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.

    Directory of Open Access Journals (Sweden)

    Helle Jensen

    Full Text Available NKG2D is a stimulatory receptor expressed by natural killer (NK cells, CD8(+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4(+ T-cells, however recently a subset of NKG2D(+ CD4(+ T-cells has been found, which is specific for human cytomegalovirus (HCMV. This particular subset of HCMV-specific NKG2D(+ CD4(+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D(+ CD4(+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4(+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA to investigate the gene expression profile of NKG2D(+ CD4(+ T-cells, generated from HCMV-primed CD4(+ T-cells. We show that the HCMV-primed NKG2D(+ CD4(+ T-cells possess a higher differentiated phenotype than the NKG2D(- CD4(+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4(+ T-cells, whereas it is produced de novo in resting CD4(+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+ CD4(+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

  8. Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer.

    Science.gov (United States)

    Nguyen, Thanh-Long M; Khurana, Shradha S; Bellone, Clifford J; Capoccia, Benjamin J; Sagartz, John E; Kesman, Russell A; Mills, Jason C; DiPaolo, Richard J

    2013-04-01

    Chronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4(+) T cells expressing a transgenic T-cell receptor specific for a peptide from the H(+)/K(+) ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer. ©2013 AACR.

  9. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

    Science.gov (United States)

    Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-06-30

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

  10. tACS phase locking of frontal midline theta oscillations disrupts working memory performance

    Directory of Open Access Journals (Sweden)

    Bankim Subhash Chander

    2016-05-01

    Full Text Available Frontal midline theta (FMT oscillations (4-8Hz are strongly related to cognitive and executive control during mental tasks such as memory processing, arithmetic problem solving or sustained attention. While maintenance of temporal order information during a working memory (WM task was recently linked to FMT phase, a positive correlation between FMT power, WM demand and WM performance was shown. However, the relationship between these measures is not well understood, and it is unknown whether purposeful FMT phase manipulation during a WM task impacts FMT power and WM performance. Here we present evidence that FMT phase manipulation mediated by transcranial alternating current stimulation (tACS can block WM demand-related FMT power increase and disrupt normal WM performance. Methods: 20 healthy volunteers were assigned to one of two groups (group A, group B and performed a 2-back task across a baseline block (block 1 and an intervention block (block 2 while 275-sensor magnetoencephalography (MEG was recorded. After no stimulation was applied during block 1, participants in group A received tACS oscillating at their individual FMT frequency over the prefrontal cortex (PFC while group B received sham stimulation during block 2. After assessing and mapping phase locking values (PLV between the tACS signal and brain oscillatory activity across the whole brain, FMT power and WM performance were assessed and compared between blocks and groups. Results: During block 2 of group A but not B, FMT oscillations showed increased PLV across task-related cortical areas underneath the frontal tACS electrode. While WM task-related FMT power increase (FMTpower and WM performance were comparable across groups in block 1, tACS resulted in lower FMTpower and WM performance compared to sham stimulation in block 2. Conclusion: tACS-related manipulation of FMT phase can disrupt WM performance and influence WM task-related FMT power increase. This finding may have

  11. A viral long terminal repeat expressed in CD4+CD8+ precursors is downregulated in mature peripheral CD4-CD8+ or CD4+CD8- T cells.

    OpenAIRE

    Paquette, Y; Doyon, L; Laperrière, A; Hanna, Z; Ball, J; Sekaly, R P; Jolicoeur, P

    1992-01-01

    The long terminal repeat from a thymotropic mouse mammary tumor virus variant, DMBA-LV, was used to drive the expression of two reporter genes, murine c-myc and human CD4, in transgenic mice. Expression was observed specifically in thymic immature cells. Expression of c-myc in these cells induced oligoclonal CD4+ CD8+ T-cell thymomas. Expression of human CD4 was restricted to thymic progenitor CD4- CD8- and CD4+ CD8+ T cells and was shut off in mature CD4+ CD8- and CD4- CD8+ T cells, known to...

  12. Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

    Science.gov (United States)

    Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

    2017-01-01

    Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co-cultured with CD4+ T cells, and the addition of a blocking antibody of CD106 significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T cells. Therefore, the results of the present study demonstrated that UC-MSC promoted the generation of IL-9 producing cells, which may be mediated, in part by CD106. The findings may act to expand understanding and knowledge of the immune modulatory role of UC-MSC. PMID:29042945

  13. Altered Intracellular ATP Production by Activated CD4+ T-Cells in Very Preterm Infants

    Directory of Open Access Journals (Sweden)

    Giulia Aquilano

    2016-01-01

    Full Text Available Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function. Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g. Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group. Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p<0.001. Twins showed lower immune activity compared to singletons (p=0.005. Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p=0.031; infants born after prolonged Premature Rupture of Membranes (pPROM showed higher CD4+ T-cell activity at birth (p=0.002 compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC in the first week of life (p=0.049. Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC.

  14. Effects of shugan jieyu panacea on behavior and levels of ACTH in plasma and T3, T4, TSH and rT3 in serum in depression rats

    International Nuclear Information System (INIS)

    Li Huijing; Li Yang; Yao Jinghui; Li Youtian

    2010-01-01

    Objective: To investigate the effects of Shugan Jieyu Panacea (SJP) on behavior and the levels of ACTH in plasma and T 3 , T 4 , TSH, rT 3 in serum in depression model rats and explore the mechanism. Methods: The model rats were lonely fed and received chronic moderate intensive unpredictable stimulation. Normal control group, depressed model group, high dosage SJP group, middle dosage SJP group, low dosage SJP group and fluoxetine group were set up. Different drugs were used in various groups for 21 d, then the body mass, sugar consumption and the behavior changes of the rats were determined and the levels of ACTH in plasma and T 3 , T 4 , TSH, rT 3 in serum were detected with radioimmunoassay. Results: Compared with normal group,the body mass was decreased (P 4 , rT 3 markedly decreased (P 3 was increased (P<0.05) in high, middle, low dosage SJP groups after treatment. At the same time, there was no obvious difference between SJP groups and fluoxetine groups. Conclusion: SJP can significantly improve the depression in rats, its mechanism may be connected with adjusting the function of HPAA and HPTA. (authors)

  15. Specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells in vivo

    International Nuclear Information System (INIS)

    Tanaka, K.; Hayakawa, H.; Sekiguchi, M.; Okada, Y.

    1977-01-01

    The specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells was examined using an in vivo assay system with hemagglutinating virus of Japan (Sendai virus) inactivated by uv light. A clear dose response was observed between the level of uv-induced unscheduled DNA synthesis of xeroderma pigmentosum cells and the amount of T4 endonuclease V activity added. The T4 enzyme was unstable in human cells, and its half-life was 3 hr. Fractions derived from an extract of Escherichia coli infected with T4v 1 , a mutant defective in the endonuclease V gene, showed no ability to restore the uv-induced unscheduled DNA synthesis of xeroderma pigmentosum cells. However, fractions derived from an extract of T4D-infected E. coli with endonuclease V activity were effective. The T4 enzyme was effective in xeroderma pigmentosum cells on DNA damaged by uv light but not in cells damaged by 4-nitroquinoline 1-oxide. The results of these experiments show that the T4 enzyme has a specific action on human cell DNA in vivo. Treatment with the T4 enzyme increased the survival of group A xeroderma pigmentosum cells after uv irradiation

  16. Cytotoxic CD4 T Cells: Differentiation, Function, and Application to Dengue Virus Infection.

    Science.gov (United States)

    Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

    2016-01-01

    Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens. Following activation, CD8 T cells can migrate to sites of infection and kill infected cells, whereas CD4 T cells contribute to the elimination of pathogens by trafficking to infected tissues and providing help to innate immune responses, B cells, as well as CD8 T cells. However, it is now evident that CD4 T cells can also perform cytotoxic functions and induce the apoptosis of target cells. Importantly, accumulating studies demonstrate that cytotoxic CD4 T cells develop following DENV infections and may play a crucial role in protecting the host from severe dengue disease. We review our current understanding of the differentiation and function of cytotoxic CD4 T cells, with a focus on DENV infection, and discuss the potential of harnessing these cells for the prevention and treatment of DENV infection and disease.

  17. CD4(+) T cells producing interleukin (IL)-17, IL-22 and interferon-? are major effector T cells in nickel allergy

    DEFF Research Database (Denmark)

    Dyring Andersen, Beatrice; Skov, Lone; Løvendorf, Marianne B

    2013-01-01

    the frequencies of CD4(+) , CD8(+) and γδ T cells producing IL-17, IL-22 and interferon (IFN)-γ in the blood and skin from nickel-allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6......-allergic patients, there was massive cellular infiltration dominated by CD4(+) T cells producing IL-17, IL-22 and IFN-γ in nickel-challenged skin but not in vehicle-challenged skin. Conclusion CD4(+) T cells producing IL-17, IL-22 and IFN-γ are important effector cells in the eczematous reactions of nickel......Background It has been suggested that interleukin (IL)-17 and IL-22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL-17 and IL-22 in human allergic contact dermatitis are unknown. Objectives To determine...

  18. Percentage and function of CD4+CD25+ re