γc deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors

Hélène Decaluwe, Morgan Taillardet, Erwan Corcuff, Ivana Munitic, Ka Wai Helen Law, Benedita Rocha, Yves Rivière, James P. Di Santo

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)9311-9316
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number20
DOIs
Publication statusPublished - 18 May 2010
Externally publishedYes

Keywords

  • Cytokine
  • Cytotoxic T lymphocyte
  • Homeostasis

ASJC Scopus subject areas

  • General

Cite this