Role of direct effects of IFN-γ on T cells in the regulation of CD8 T cell homeostasis

K Tewari, Y Nakayama, M Suresh - The Journal of Immunology, 2007 - journals.aai.org
K Tewari, Y Nakayama, M Suresh
The Journal of Immunology, 2007journals.aai.org
It is well recognized that IFN-γ 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-γ is sorely
incomplete. Specifically, it is unclear whether regulation of CD8 T cell homeostasis occurs
by a T cell intrinsic IFN-γ pathway. In this study, we have determined the role of the direct
effects of IFN-γ on T cells in regulating the expansion, contraction, and memory phases of …
Abstract
It is well recognized that IFN-γ 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-γ is sorely incomplete. Specifically, it is unclear whether regulation of CD8 T cell homeostasis occurs by a T cell intrinsic IFN-γ pathway. In this study, we have determined the role of the direct effects of IFN-γ 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-γ 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-γR signaling in T cells. These findings have clarified fundamental features of control of T cell homeostasis by IFN-γ in the context of CD8 T cell memory and protective immunity.
journals.aai.org