by
Katherine T. Fay;
Deena B. Chihade;
Ching-Wen Chen;
Nathan J. Klingensmith;
John D. Lyons;
Kimberly Ramonell;
Zhe Liang;
Craig Coopersmith;
Mandy Ford
CD43 is a large transmembrane protein involved in T cell activation. Previous studies of CD43-/-mice in viral models have demonstrated a role for CD43 in Th1/Th2 skewing, activation of Foxp3+ Treg, and T cell apoptosis. However, the role of CD43 during sepsis has never been tested. Thus, we interrogated the role of CD43 during sepsis using a murine cecal ligation and puncture (CLP) model, and found that CD43-/-mice demonstrated significantly worsened mortality compared to B6 mice following CLP. Phenotypic analysis of splenocytes isolated 24 h after septic insult revealed significantly increased apoptosis of central memory cells in both CD4+and CD8+T cell compartments in CD43-/-septic mice compared to WT septic mice. Furthermore, CD43-/-septic mice exhibited a prominent Th2 skewing following sepsis relative to WT septic mice, as evidenced by a significant decrease in the frequency of IL-2+CXCR3+TH1 cells as a significant increase in the frequency of IL-4+CCR4+TH2 cells. Finally, septic CD43-/-animals contained significantly fewer CD25+Foxp3+TRegcells as compared to WT septic animals. Importantly, depleting CD25+Treg eliminated the increased mortality observed in CD43-/-mice. Taken together, these data demonstrate an important role of CD43 in modulating immune dysregulation and mortality following sepsis.