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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...

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Autores principales: Löhning, Max, Hegazy, Ahmed N., Pinschewer, Daniel D., Busse, Dorothea, Lang, Karl S., Höfer, Thomas, Radbruch, Andreas, Zinkernagel, Rolf M., Hengartner, Hans
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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.
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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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