Regulatory T cell-mediated suppression: potential role of ICER.
How regulatory T (TR) cells dampen T cell responses remains unclear. Multiple modes of action have been proposed, including cell contact-dependent and/or cytokine-dependent mechanisms. Suppression may involve direct contact between TR cells and responder T cells. Alternatively, TR cells may act on dendritic cells to reduce their ability to prime T cells by modulating costimulation, inducing the secretion of suppressive cytokines or the increase of tryptophan metabolism. Here, we review emerging, novel mechanisms involved in contact-dependent, TR-mediated suppression of IL-2 production in responder CD25- T lymphocytes and the potential involvement of inducible cAMP early repressor (ICER) in this suppression. Finally, cytokines such as TGF-beta and IL-10, produced by TR cells or other cells, may exert local suppression, which can be conveyed by basic mechanism(s) acting in a similar manner as contact-dependent, TR-mediated suppression.
Bodor
Josef
J
Department of Medicine, Columbia University, College of Physicians and Surgeons, 1130 St. Nicholas Ave., New York, NY 10032, USA. jb2562@columbia.edu
Fehervari
Zoltan
Z
Diamond
Betty
B
Sakaguchi
Shimon
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D060908:CTLA-4 Antigen; D051786:Cyclic AMP Response Element Modulator / Q000502:physiology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018448:Models, Immunological; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; C497410:CREM protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D016212:Transforming Growth Factor beta; D051786:Cyclic AMP Response Element Modulator