title: IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.
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.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Motoko Y
authors.initials: MY
authors.lastname: Kimura
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Pobezinsky
authors.forename: Terry I
authors.initials: TI
authors.lastname: Guinter
authors.forename: Julien
authors.initials: J
authors.lastname: Thomas
authors.forename: Anthony
authors.initials: A
authors.lastname: Adams
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors
chemical_list: D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; C576410:interleukin-7, mouse; D007371:Interferon-gamma