title: Differential Responsiveness of Innate-like IL-17- and IFN-γ-Producing γδ T Cells to Homeostatic Cytokines.
abstract: γδ T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing γδ T (γδT-17) and IFN-γ-producing γδ T (γδT-IFNγ) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional γδ T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like γδT-17 and γδT-IFNγ cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional γδ T cells, but they do not monopolize the same cytokine. γδT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. γδT-IFNγ cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional γδ T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive αβ T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that γδ T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes.
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Corpuz
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
authors.forename: Jessica
authors.initials: J
authors.lastname: Stolp
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Republic of Korea;
authors.forename: Hee-Ok
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Pinget
authors.affiliation: Molecular Genetics of Cancer Division and Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia; and.
authors.forename: Daniel H D
authors.initials: DH
authors.lastname: Gray
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Republic of Korea;
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2010, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2010, Australia k.webster@garvan.org.au.
authors.forename: Kylie E
authors.initials: KE
authors.lastname: Webster
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma