Increased circulating regulatory T cells (CD4+CD25+CD127-) contribute to lymphocyte anergy in septic shock patients

Purpose: Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to mortality. We investigated whether CD4(+)CD25(+) regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis. Method: Observational study in septic shock patients and experimental study in mice. Results: We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4(+)CD25(+)CD127(-)Foxp3(+)). In patients the increased circulating Treg percentage significantly correlated with a decreased lymphoproliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response. Conclusion: The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis.