|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|
|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|
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.|