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{gamma}c deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors.

Abstract : Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common gamma chain (gamma(c)) are critical for the generation and peripheral homeostasis of naive and memory T cells. Recently, we demonstrated that effector functions fail to develop in CD4(+) T cells that differentiate in the absence of gamma(c). To assess the role of gamma(c) cytokines in cell-fate decisions that condition effector versus memory CD8(+) T cell generation, we compared the response of CD8(+) T cells from gamma(c)(+) or gamma(c)(-) P14 TCR transgenic mice after challenge with lymphocytic choriomeningitis virus. The intrinsic IL-7-dependent survival defect of gamma(c)(-) naive CD8(+) T cells was corrected by transgenic expression of human Bcl-2. We demonstrated that although gamma(c)-dependent signals are dispensable for the initial expansion and the acquisition of cytotoxic functions following antigenic stimulation, they condition the terminal proliferation and differentiation of CD8(+) effector T cells (i.e., KLRG1(high) CD127(low) short-lived effector T cells) via the transcription factor, T-bet. Moreover, the gamma(c)-dependent signals that are critical for memory T cell formation are not rescued by Bcl2 overexpression. Together, these data reveal an unexpected divergence in the requirement for gamma(c) cytokines in the differentiation of CD4(+) versus CD8(+) cytotoxic T lymphocytes.
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Contributor : Mireille Gau Connect in order to contact the contributor
Submitted on : Thursday, June 3, 2010 - 10:56:11 AM
Last modification on : Tuesday, May 31, 2022 - 10:20:14 AM

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Hélène Decaluwe, Morgan Taillardet, Erwan Corcuff, Ivana Munitic, Helen K W Law, et al.. {gamma}c deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors.. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107 (20), pp.9311-6. ⟨10.1073/pnas.0913729107⟩. ⟨pasteur-00488854⟩



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