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

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

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 107 (2010), 20; 9311-9316

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA