Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 1, Pages 207-215Publisher
WILEY
DOI: 10.1002/eji.200838748
Keywords
CD161; ROR gamma t; TGF-beta; Th17
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Funding
- EU [FP6-LSBH-CT-2006-018861]
- INNOCHEM [FP6LSHB-CT-2005-518167]
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Human Th17 clones and circulating Th17 cells showed lower susceptibility to the antiproliferative effect of TGF-beta than Th1 and Th2 clones or circulating Th1-oriented T cells, respectively. Accordingly, human Th17 cells exhibited lower expression of clusterin, and higher Bcl-2 expression and reduced apoptosis in the presence of TGF-beta, in comparison with Th1 cells. Umbilical cord blood naive CD161(+)CD4(+) T cells, which contain the precursors of human Th17 cells, differentiated into IL-17A-producing cells only in response to IL-1 beta plus IL-23, even in serum-free cultures. TGF-beta had no effect on constitutive ROR gamma t expression by umbilical cord blood CD161(+) T cells but it increased the relative proportions of CD161(+) T cells differentiating into Th17 cells in response to IL-1 beta plus IL-23, whereas under the same conditions it inhibited both T-bet expression and Th1 development. These data suggest that TGF-beta is not critical for the differentiation of human Th17 cells, but indirectly favors their expansion because Th17 cells are poorly susceptible to its suppressive effects.
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