Increased mortality in CD43-deficient mice during sepsis

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(+) T(H)1 cells as a significant increase in the frequency of IL-4(+) CCR4(+) T(H)2 cells. Finally, septic CD43(-/-) animals contained significantly fewer CD25(+) Foxp3(+) TReg cells 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.