FOXP3+ CD4+ Tregs lose suppressive potential but remain anergic during transient inflammation in human.

Tregs are crucial in controlling inflammation. Although the transcription factor FOXP3 is the most applicable phenotype marker of Tregs, it does not indisputably characterize suppressive function during T-cell activation in vitro. A question that remains is: what is the functionality of FOXP3(+) T cells during inflammation in vivo? We studied FOXP3(+) T cells in a human model of acute inflammation due to cardiac surgery. Twenty-five children who underwent cardiac surgery for correction of a septum defect were included. Following surgery, we observed a transient systemic inflammatory response accompanied by an increased proportion of CD25(bright) T cells with sustained Treg phenotype. During this transient immune activation, both the percentage of CD4(+) FOXP3(+) cells and the level of expression of FOXP3 in the CD4(+) CD25(bright) CD127(low) population increased. While Tregs remained present during systemic inflammation and continued to be anergic, the capacity to suppress effector T cells was reduced. The reduced suppressive state of Tregs could be induced in vitro by plasma obtained during the peak of inflammation after surgery. These data show that inflammation inhibits Treg function through soluble factors present in plasma. These results underscore the functional role of FOXP3(+) Tregs during inflammation in vivo.