FOXP3+CD4+CD25+ adaptive regulatory T cells express cyclooxygenase-2 and suppress effector T cells by a prostaglandin E2-dependent mechanism

CD4(+)CD25(+) regulatory T (T-R) cells suppress effector T cells by partly unknown mechanisms.' In this study, we describe a population of human suppressive CD4(+)CD25(+) adaptive TR (TR adapt) cells induced in vitro that express cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. TRadapt cells produce PGE(2) and suppress effector T cell responses in a manner that is reversed by COX inhibitors and PGE2 receptor-specific antagonists. In resting CD4(+)CD25(-) T cells, treatment with PGE2 induced FOXP3 expression. Thus, autocrine and paracrine effects of PGE(2) produced by COX-2-positive T-R(adapt) cells may be responsible for both the FOXP3(+) phenotype and the mechanism used by these cells to suppress effector T cells.