Cutting Edge: 2B4-Mediated Coinhibition of CD4⁺ T Cells Underlies Mortality in Experimental Sepsis.

ABSTRACT: Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8⁺ T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4⁺ T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4⁺

SUBMITTER: Chen CW 

PROVIDER: S-EPMC5587400 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature