IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.

TitleIL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.
Publication TypeJournal Article
Year of Publication2013
AuthorsKimura MY, Pobezinsky LA, Guinter TI, Thomas J, Adams A, Park J-H, Tai X, Singer A
JournalNat Immunol
Volume14
Issue2
Pagination143-51
Date Published2013 Feb
ISSN1529-2916
KeywordsAnimals, CD8-Positive T-Lymphocytes, Cell Death, Cell Proliferation, Cell Survival, Gene Expression Regulation, Homeostasis, Interferon-gamma, Interleukin-7, Lymphocyte Activation, Mice, Mice, Transgenic, Receptors, Antigen, T-Cell, Signal Transduction, Time Factors
Abstract

The maintenance of naive CD8(+) T cells is necessary for lifelong immunocompetence but for unknown reasons requires signaling via both interleukin 7 (IL-7) and the T cell antigen receptor (TCR). We now report that naive CD8(+) T cells required IL-7 signaling to be intermittent, not continuous, because prolonged IL-7 signaling induced naive CD8(+) T cells to proliferate, produce interferon-γ (IFN-γ) and undergo IFN-γ-triggered cell death. Homeostatic engagement of the TCR interrupted IL-7 signaling and thereby supported the survival and quiescence of CD8(+) T cells. However, CD8(+) T cells with insufficient TCR affinity for self ligands received prolonged IL-7 signaling and died during homeostasis. In this study we identified regulation of the duration of IL-7 signaling by homeostatic engagement of the TCR as the basis for in vivo CD8(+) T cell homeostasis.

DOI10.1038/ni.2494
Alternate JournalNat. Immunol.
PubMed ID23242416