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Repeated stimulation of CD4 effector T cells can limit their protective function

Chronic infections often result in CD8 T-cell deletion or functional nonresponsiveness. However, to date no definitive studies have attempted to determine the impact of repeated T cell receptor stimulation on CD4 effector T cell generation. We have determined that when antigen presentation is limite...

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Autores principales: Jelley-Gibbs, Dawn M., Dibble, John P., Filipson, Svetlana, Haynes, Laura, Kemp, Roslyn A., Swain, Susan L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213138/
https://www.ncbi.nlm.nih.gov/pubmed/15795235
http://dx.doi.org/10.1084/jem.20041852
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author Jelley-Gibbs, Dawn M.
Dibble, John P.
Filipson, Svetlana
Haynes, Laura
Kemp, Roslyn A.
Swain, Susan L.
author_facet Jelley-Gibbs, Dawn M.
Dibble, John P.
Filipson, Svetlana
Haynes, Laura
Kemp, Roslyn A.
Swain, Susan L.
author_sort Jelley-Gibbs, Dawn M.
collection PubMed
description Chronic infections often result in CD8 T-cell deletion or functional nonresponsiveness. However, to date no definitive studies have attempted to determine the impact of repeated T cell receptor stimulation on CD4 effector T cell generation. We have determined that when antigen presentation is limited to 2 d, optimum in vitro CD4 effector generation is achieved. Alternatively, repeated stimulation results in decreased CD4 effector expansion, decreased cytokine production, and altered migration. Similarly, functionally impaired effectors develop in vivo when antigen-pulsed antigen-presenting cells are replenished every 24 h during a primary immune response. CD4 effectors that are generated with repeated stimulation provide no protection during influenza infection, and have an impaired ability to provide cognate help to B cells. These results suggest that duration of antigen presentation dictates CD4 effector function, and repeated T cell receptor stimulation in vitro and in vivo that exceeds an optimal threshold results in effectors with impaired function.
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spelling pubmed-22131382008-03-11 Repeated stimulation of CD4 effector T cells can limit their protective function Jelley-Gibbs, Dawn M. Dibble, John P. Filipson, Svetlana Haynes, Laura Kemp, Roslyn A. Swain, Susan L. J Exp Med Article Chronic infections often result in CD8 T-cell deletion or functional nonresponsiveness. However, to date no definitive studies have attempted to determine the impact of repeated T cell receptor stimulation on CD4 effector T cell generation. We have determined that when antigen presentation is limited to 2 d, optimum in vitro CD4 effector generation is achieved. Alternatively, repeated stimulation results in decreased CD4 effector expansion, decreased cytokine production, and altered migration. Similarly, functionally impaired effectors develop in vivo when antigen-pulsed antigen-presenting cells are replenished every 24 h during a primary immune response. CD4 effectors that are generated with repeated stimulation provide no protection during influenza infection, and have an impaired ability to provide cognate help to B cells. These results suggest that duration of antigen presentation dictates CD4 effector function, and repeated T cell receptor stimulation in vitro and in vivo that exceeds an optimal threshold results in effectors with impaired function. The Rockefeller University Press 2005-04-04 /pmc/articles/PMC2213138/ /pubmed/15795235 http://dx.doi.org/10.1084/jem.20041852 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Jelley-Gibbs, Dawn M.
Dibble, John P.
Filipson, Svetlana
Haynes, Laura
Kemp, Roslyn A.
Swain, Susan L.
Repeated stimulation of CD4 effector T cells can limit their protective function
title Repeated stimulation of CD4 effector T cells can limit their protective function
title_full Repeated stimulation of CD4 effector T cells can limit their protective function
title_fullStr Repeated stimulation of CD4 effector T cells can limit their protective function
title_full_unstemmed Repeated stimulation of CD4 effector T cells can limit their protective function
title_short Repeated stimulation of CD4 effector T cells can limit their protective function
title_sort repeated stimulation of cd4 effector t cells can limit their protective function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213138/
https://www.ncbi.nlm.nih.gov/pubmed/15795235
http://dx.doi.org/10.1084/jem.20041852
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