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Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors
Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation m...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234365/ https://www.ncbi.nlm.nih.gov/pubmed/18195073 http://dx.doi.org/10.1084/jem.20071855 |
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author | Löhning, Max Hegazy, Ahmed N. Pinschewer, Daniel D. Busse, Dorothea Lang, Karl S. Höfer, Thomas Radbruch, Andreas Zinkernagel, Rolf M. Hengartner, Hans |
author_facet | Löhning, Max Hegazy, Ahmed N. Pinschewer, Daniel D. Busse, Dorothea Lang, Karl S. Höfer, Thomas Radbruch, Andreas Zinkernagel, Rolf M. Hengartner, Hans |
author_sort | Löhning, Max |
collection | PubMed |
description | Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon γ–secreting T helper (Th) type 1 and interleukin (IL)-4– or IL-10–secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells. |
format | Text |
id | pubmed-2234365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22343652008-07-21 Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors Löhning, Max Hegazy, Ahmed N. Pinschewer, Daniel D. Busse, Dorothea Lang, Karl S. Höfer, Thomas Radbruch, Andreas Zinkernagel, Rolf M. Hengartner, Hans J Exp Med Brief Definitive Reports Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon γ–secreting T helper (Th) type 1 and interleukin (IL)-4– or IL-10–secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells. The Rockefeller University Press 2008-01-21 /pmc/articles/PMC2234365/ /pubmed/18195073 http://dx.doi.org/10.1084/jem.20071855 Text en Copyright © 2008, 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 Reports Löhning, Max Hegazy, Ahmed N. Pinschewer, Daniel D. Busse, Dorothea Lang, Karl S. Höfer, Thomas Radbruch, Andreas Zinkernagel, Rolf M. Hengartner, Hans Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title | Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title_full | Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title_fullStr | Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title_full_unstemmed | Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title_short | Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors |
title_sort | long-lived virus-reactive memory t cells generated from purified cytokine-secreting t helper type 1 and type 2 effectors |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234365/ https://www.ncbi.nlm.nih.gov/pubmed/18195073 http://dx.doi.org/10.1084/jem.20071855 |
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