The common γ chain cytokines interleukin (IL)-2 and IL-7 are important regulators of T cell homeostasis. Although IL-2 is implicated in the acute phase of the T cell response, IL-7 is important for memory T cell survival. We asked whether regulated responsiveness to these growth factors is determined by temporal expression of the cytokine-specific IL-2 receptor (R) α and IL-7Rα chains. We demonstrate that IL-2Rα is expressed early after priming in T cell receptor–transgenic CD4+ T cells, whereas IL-7Rα expression is lost. In the later stage of the response, IL-7Rα is reexpressed while IL-2Rα expression is silenced. This reciprocal pattern of IL-2Rα/IL-7Rα expression is disturbed when CD4+ T cells are primed in the absence of IL-2 signals. Primed IL-2−/− or CD25−/− (IL-2Rα−/−) CD4+ T cells, despite showing normal induction of activation markers and cell division, fail to reexpress IL-7Rα late in the response. Because the generation of CD4+ memory T cells is dependent on IL-7–IL-7Rα interactions, primed IL-2−/− or CD25−/− CD4+ T cells develop poorly into long-lived memory cells. Retrovirus-mediated expression of IL-7Rα in IL-2−/− T cells restores their capacity for long-term survival. These results identify IL-2 as a factor regulating IL-7Rα expression and, consequently, memory T cell homeostasis in vivo.
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19 March 2007
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February 20 2007
Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7Rα–expressing cells
Hans Dooms,
Hans Dooms
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
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Kristen Wolslegel,
Kristen Wolslegel
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
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Patricia Lin,
Patricia Lin
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
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Abul K. Abbas
Abul K. Abbas
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
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Hans Dooms
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
Kristen Wolslegel
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
Patricia Lin
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
Abul K. Abbas
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143
CORRESPONDENCE Abul K. Abbas: [email protected]
Abbreviations used: CFSE, carboxyfluorescein diacetate succinimidyl ester; γc, γ chain; MFI, mean fluorescence intensity.
Received:
November 15 2006
Accepted:
January 25 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (3): 547–557.
Article history
Received:
November 15 2006
Accepted:
January 25 2007
Citation
Hans Dooms, Kristen Wolslegel, Patricia Lin, Abul K. Abbas; Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7Rα–expressing cells . J Exp Med 19 March 2007; 204 (3): 547–557. doi: https://doi.org/10.1084/jem.20062381
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