Journal
NATURE IMMUNOLOGY
Volume 14, Issue 2, Pages 143-151Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2494
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Funding
- Uehara Memorial Foundation
- Kanae Foundation
- US National Institutes of Health, National Cancer Institute, Center for Cancer Research
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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-gamma (IFN-gamma) and undergo IFN-gamma-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.
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