IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo

The Journal of Experimental Medicine
Gabriel R Starbeck-MillerJohn T Harty

Abstract

TCR ligation and co-stimulation induce cellular division; however, optimal accumulation of effector CD8 T cells requires direct inflammatory signaling by signal 3 cytokines, such as IL-12 or type I IFNs. Although in vitro studies suggest that IL-12/type I IFN may enhance T cell survival or early proliferation, the mechanisms underlying optimal accumulation of CD8 T cells in vivo are unknown. In particular, it is unclear if disparate signal 3 cytokines optimize effector CD8 T cell accumulation by the same mechanism and how these inflammatory cytokines, which are transiently produced early after infection, affect T cell accumulation many days later at the peak of the immune response. Here, we show that transient exposure of CD8 T cells to IL-12 or type I IFN does not promote survival or confer an early proliferative advantage in vivo, but rather sustains surface expression of CD25, the high-affinity IL-2 receptor. This prolongs division of CD8 T cells in response to basal IL-2, through activation of the PI3K pathway and expression of FoxM1, a positive regulator of cell cycle progression genes. Thus, signal 3 cytokines use a common pathway to optimize effector CD8 T cell accumulation through a temporally orchestrated sequence of c...Continue Reading

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Methods Mentioned

BETA
flow cytometry
transgenic
FACS
FCS

Software Mentioned

GSEA
GeneChip Operating
DAVID
Database for Annotation , Visualization , and Integrated Disco...

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