1. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.
- Author
-
Ching-wen Chen, Mittal, Rohit, Klingensmith, Nathan J., Burd, Eileen M., Terhorst, Cox, Martin, Greg S., Coopersmith, Craig M., and Ford, Mandy L.
- Subjects
- *
SEPSIS , *IMMUNOLOGY , *KILLER cells , *T cells , *VIRUS diseases - 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+ T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4+ T cells in mediating immune dysregulation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF