Publication
γ
c
deficiency precludes CD8
+
T cell memory despite formation of potent T cell effectors
Publisher:
Proceedings of the National Academy of Sciences
Date:
03-05-2010
DOI:
10.1073/PNAS.0913729107
Abstract: Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common γ chain (γ 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 γ c . To assess the role of γ c cytokines in cell-fate decisions that condition effector versus memory CD8 + T cell generation, we compared the response of CD8 + T cells from γ c + or γ c − P14 TCR transgenic mice after challenge with lymphocytic choriomeningitis virus. The intrinsic IL-7-dependent survival defect of γ c − naive CD8 + T cells was corrected by transgenic expression of human Bcl-2. We demonstrated that although γ 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 γ c -dependent signals that are critical for memory T cell formation are not rescued by Bcl2 overexpression. Together, these data reveal an unexpected ergence in the requirement for γ c cytokines in the differentiation of CD4 + versus CD8 + cytotoxic T lymphocytes.