Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 4, Pages 2115-2125Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.4.2115
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Funding
- NIAID NIH HHS [AI059804] Funding Source: Medline
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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-gamma R 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.
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