Innate immune cells contribute to the IFN-gamma-dependent regulation of antigen-specific CD8+ T cell homeostasis.
IFN-gamma has a dual function in the regulation of T cell homeostasis. It promotes the expansion of effector T cells and simultaneously programs their contraction. The cellular mechanisms leading to this functional dichotomy of IFN-gamma have not been identified to date. In this study we show: 1) that expansion of wild-type CD8+ T cells is defective in IFN-gamma-deficient mice but increased in IFN-gammaR-deficient mice; and 2) that contraction of the effector CD8+ T cell pool is impaired in both mouse strains. Furthermore, we show that CD11b+ cells responding to IFN-gamma are sufficient to limit CD8+ T cell expansion and promote contraction. The data presented here reveal that IFN-gamma directly promotes CD8+ T cell expansion and simultaneously induces suppressive functions in CD11b+ cells that counter-regulate CD8+ T cell expansion, promote contraction, and limit memory formation. Thus, innate immune cells contribute to the IFN-gamma-dependent regulation of Ag-specific CD8+ T cell homeostasis.
Sercan
Ozen
O
German Cancer Research Center, Heidelberg, Germany.
Hämmerling
Günter J
GJ
Arnold
Bernd
B
Schüler
Thomas
T
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004527:Egg Proteins / Q000276:immunology; D006706:Homeostasis; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D000096743:Interferon gamma Receptor
D039481:CD11b Antigen; D004527:Egg Proteins; D007371:Interferon-gamma; D010047:Ovalbumin; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C110366:OVA-8