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 T(R) (T(R)(adapt)) cells induced in vitro that express cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. T(R)(adapt) cells produce PGE(2) and suppress effector T cell responses in a manner that is reversed by COX inhibitors and PGE(2) receptor-specific antagonists. In resting CD4+CD25- T cells, treatment with PGE(2) 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.
Mahic
Milada
M
The Biotechnology Centre, Ullevaal University Hospital, University of Oslo, N-0317 Oslo, Norway.
Yaqub
Sheraz
S
Johansson
C Christian
CC
Taskén
Kjetil
K
Aandahl
Einar M
EM
D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004768:Enterotoxins / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D011448:Prostaglandin Antagonists / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
D052246:Cyclooxygenase 2 Inhibitors; D004768:Enterotoxins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D011448:Prostaglandin Antagonists; D015375:Receptors, Interleukin-2; D018078:Receptors, Prostaglandin E; C031818:enterotoxin B, staphylococcal; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D015232:Dinoprostone