Transforming growth factor-beta-induced regulatory T cells referee inflammatory and autoimmune diseases.
Naturally occurring CD4+CD25+ regulatory T cells mediate immune suppression to limit immunopathogenesis associated with chronic inflammation, persistent infections and autoimmune diseases. Their mode of suppression is contact-dependent, antigen-nonspecific and involves a nonredundant contribution from the cytokine transforming growth factor (TGF)-beta. Not only can TGF-beta mediate cell-cell suppression between the regulatory T cells and CD4+CD25- or CD8+ T cells, but new evidence also reveals its role in the conversion of CD4+CD25- T cells, together with TCR antigen stimulation, into the regulatory phenotype. Elemental to this conversion process is induction of expression of the forkhead transcription factor, Foxp3. This context-dependent coercion of naive CD4+ T cells into a powerful subset of regulatory cells provides a window into potential manipulation of these cells to orchestrate therapeutic intervention in diseases characterized by inadequate suppression, as well as a promising means of controlling pathologic situations in which excessive suppression dominates.
Wahl
Sharon M
SM
Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Disease, National Institutes of Health, Bethesda, Maryland, USA. smwahl@dir.nidcr.nih.gov
Chen
Wanjun
W
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D001249:Asthma / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000502:physiology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta
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