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Gamma(c) deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors. (CROSBI ID 243749)

Prilog u časopisu | izvorni znanstveni rad

Decaluwe, H. ; Taillardet, M. ; Corcuff, E. ; Munitić, Ivana ; Law, H. K. W. ; Rocha, B. ; Riviere, Y. ; Di Santo, J.P. 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, 107 (2010), 20; 9311-9316. doi: 10.1073/pnas.0913729107

Podaci o odgovornosti

Decaluwe, H. ; Taillardet, M. ; Corcuff, E. ; Munitić, Ivana ; Law, H. K. W. ; Rocha, B. ; Riviere, Y. ; Di Santo, J.P.

engleski

Gamma(c) deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors.

Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common γ chain (γc) 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 γc. To assess the role of γc cytokines in cell-fate decisions that condition effector versus memory CD8+ T cell generation, we compared the response of CD8+ T cells from γc+ or γc− P14 TCR transgenic mice after challenge with lymphocytic choriomeningitis virus. The intrinsic IL-7-dependent survival defect of γc− naive CD8+ T cells was corrected by transgenic expression of human Bcl-2. We demonstrated that although γc-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., KLRG1high CD127low short-lived effector T cells) via the transcription factor, T-bet. Moreover, the γc-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 γc cytokines in the differentiation of CD4+ versus CD8+ cytotoxic T lymphocytes.

CD8+ T cells, memory responses, common gamma chain, effector responses

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Podaci o izdanju

107 (20)

2010.

9311-9316

objavljeno

0027-8424

1091-6490

10.1073/pnas.0913729107

Povezanost rada

Biologija

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