Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.
J Immunol
; 199(6): 1961-1966, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28768726
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Linfócitos T CD4-Positivos
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Subpopulações de Linfócitos
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Sepse
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Família de Moléculas de Sinalização da Ativação Linfocitária
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2017
Tipo de documento:
Article