T helper 3 cell (Th3) have different cytokine requirements for their growth from CD25+ CD4+ Treg cells. The survival of CD25+ CD4+ Treg cells is dependent upon interleukin 2 (IL-2), while in vitro differentiation of Th3 cells is enhanced by transforming growth factor beta (TGF-β), IL-4, and IL-10.
Findings suggest that Th3 cells are a different linage from naturally arising CD25+ CD4+ Treg cells, but it is still unclear whether Th3 cells are the same as induced Treg cells because of the lack of a specific marker for Th3 cells. It was previously shown that TGF-β was produced by intestinal dendritic cells, which has been considered to be the source of cytokines for the induction of Th3 cells in the intestine. Additionally, since TGF-β production was induced by cytotoxic T-lymphocyte antigen 4 (CTLA-4), which is constitutively expressed on naturally arising Treg cells, it is possible that TGF-β production from Treg cells through CTLA-4–mediated signaling may stimulate the differentiation of both induced Treg cells and Th3 cells.
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