Th3

Th3 cells have different cytokine requirements for their growth from CD25+ CD4+ Treg cells. The survival of CD25+ CD4+ Treg cells is dependent upon IL-2 (1), while in vitro differentiation of Th3 cells is enhanced by 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 DCs (2,3), 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 CTLA-4, which is constitutively expressed on naturally arising Treg cells (4), 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.

References

1.Sakaguchi S, Ono M, Setoguchi R, et al. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006;212:8–27.

2. Johansson C, Kelsall BL. Phenotype and function of intestinal dendritic cells. Semin Immunol. 2005;17:284–294.

3. Iwasaki A. Mucosal dendritic cells. Annu Rev Immunol. 2007;25: 381–418.

4. Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med. 2003;198:1875–1886.