Role of direct effects of IFN-gamma on T cells in the regulation of CD8 T cell homeostasis.
It is well recognized that IFN-gamma plays a critical role in the control of CD8 T cell expansion and contraction during immune responses to several intracellular pathogens. However, our understanding of the mechanisms underlying the regulation of T cell fate by IFN-gamma is sorely incomplete. Specifically, it is unclear whether regulation of CD8 T cell homeostasis occurs by a T cell intrinsic IFN-gamma pathway. In this study, we have determined the role of the direct effects of IFN-gamma on T cells in regulating the expansion, contraction, and memory phases of the polyclonal CD8 T cell response to an acute viral infection. Using two complementary approaches we demonstrate that the direct effects of IFN-gamma suppress IL-7R expression on Ag-specific effector CD8 T cells, but clonal expansion or deletion of activated CD8 T cells in vivo can occur in the apparent absence of IFN-gammaR signaling in T cells. These findings have clarified fundamental features of control of T cell homeostasis by IFN-gamma in the context of CD8 T cell memory and protective immunity.
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Kavita
K
Tewari
Yumi
Y
Nakayama
M
M
Suresh
D000208:Acute Disease; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020395:Receptors, Interleukin-7 / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma