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 lympho-proliferative 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.
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 shockpatients 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 lympho-proliferative 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.
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