Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta.
Recent studies have shown that TGF-beta together with IL-6 induce the differentiation of IL-17-producing T cells (Th17) T cells. We therefore examined whether CD4(+)CD25(+)Foxp3(+) regulatory T cells, i.e., cells previously shown to produce TGF-beta, serve as Th17 inducers. We found that upon activation purified CD25(+) T cells (or sorted GFP(+) T cells obtained from Foxp3-GFP knockin mice) produce high amounts of soluble TGF-beta and when cultured with CD4(+)CD25(-)Foxp3(-) T cells in the presence of IL-6 induce the latter to differentiate into Th17 cells. Perhaps more importantly, upon activation, CD4(+)CD25(+)Foxp3(+)(GFP(+)) T cells themselves differentiate into Th17 cells in the presence of IL-6 (and in the absence of exogenous TGF-beta). These results indicate that CD4(+)CD25(+)Foxp3(+) regulatory T cells can function as inducers of Th17 cells and can differentiate into Th17 cells. They thus have important implications to our understanding of regulatory T cell function and their possible therapeutic use.
Xu
Lili
L
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kitani
Atsushi
A
Fuss
Ivan
I
Strober
Warren
W
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000502:physiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000378:metabolism*; D015850:Interleukin-6 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D016212:Transforming Growth Factor beta