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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 03 May 2010

Decaluwe H, Taillardet M, Corcuff E, Munitic I, Law HK, Rocha B, Rivière Y, Di Santo JP

Link to Pubmed [PMID] – 20439728

Proc. Natl. Acad. Sci. U.S.A. 2010 May;107(20):9311-6

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.

http://www.ncbi.nlm.nih.gov/pubmed/20439728