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Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production
The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV a...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194206/ https://www.ncbi.nlm.nih.gov/pubmed/12963692 http://dx.doi.org/10.1084/jem.20021288 |
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author | Topp, Max S. Riddell, Stanley R. Akatsuka, Yoshiki Jensen, Michael C. Blattman, Joseph N. Greenberg, Philip D. |
author_facet | Topp, Max S. Riddell, Stanley R. Akatsuka, Yoshiki Jensen, Michael C. Blattman, Joseph N. Greenberg, Philip D. |
author_sort | Topp, Max S. |
collection | PubMed |
description | The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8(+) T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8(+) T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28(−) CD8(+) T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28(−) CD8(+) CMV- and HIV-specific CD8(+) T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory/effector CD8(+) T cells represents a decisive step in establishing regulation of responding CD8(+) T cells, increasing the dependence on CD4(+) Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8(+) T cells. |
format | Text |
id | pubmed-2194206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21942062008-04-11 Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production Topp, Max S. Riddell, Stanley R. Akatsuka, Yoshiki Jensen, Michael C. Blattman, Joseph N. Greenberg, Philip D. J Exp Med Brief Definitive Report The control of many persistent viral infections by Ag-specific cytolytic CD8(+) T cells requires a concurrent virus-specific CD4(+) Th cell response. This reflects in part a requirement of activated effector CD8(+) T cells for paracrine IL-2 production as a growth and survival factor. In human CMV and HIV infection, the majority of differentiated virus-specific CD8(+) T cells notably lose the ability to produce IL-2 but also lose expression of CD28, a costimulatory molecule. Analysis of the fraction of memory CD8(+) T cells that continue to express CD28 revealed these cells retain the ability to produce IL-2. Therefore, we examined if IL-2 production by CD28(−) CD8(+) T cells could be restored by introduction of a constitutively expressed CD28 gene. Expression of CD28 in CD28(−) CD8(+) CMV- and HIV-specific CD8(+) T cells reconstituted the ability to produce IL-2, which could sustain an autocrine proliferative response after Ag recognition. These results suggest that the loss of CD28 expression during differentiation of memory/effector CD8(+) T cells represents a decisive step in establishing regulation of responding CD8(+) T cells, increasing the dependence on CD4(+) Th for proliferation after target recognition, and has implications for the treatment of viral disease with adoptively transferred CD8(+) T cells. The Rockefeller University Press 2003-09-15 /pmc/articles/PMC2194206/ /pubmed/12963692 http://dx.doi.org/10.1084/jem.20021288 Text en Copyright © 2003, 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 | Brief Definitive Report Topp, Max S. Riddell, Stanley R. Akatsuka, Yoshiki Jensen, Michael C. Blattman, Joseph N. Greenberg, Philip D. Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title | Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title_full | Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title_fullStr | Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title_full_unstemmed | Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title_short | Restoration of CD28 Expression in CD28(−) CD8(+) Memory Effector T Cells Reconstitutes Antigen-induced IL-2 Production |
title_sort | restoration of cd28 expression in cd28(−) cd8(+) memory effector t cells reconstitutes antigen-induced il-2 production |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194206/ https://www.ncbi.nlm.nih.gov/pubmed/12963692 http://dx.doi.org/10.1084/jem.20021288 |
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