Title | IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Kimura, MY, Pobezinsky, LA, Guinter, TI, Thomas, J, Adams, A, Park, J-H, Tai, X, Singer, A |
Journal | Nat Immunol |
Volume | 14 |
Issue | 2 |
Pagination | 143-51 |
Date Published | 2013 Feb |
Keywords | Animals, 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. |
Alternate Journal | Nat. Immunol. |
Veterinary and Animal Sciences