T helper 3 cell

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T helper 3 cells (Th3) are white blood cells of the lymphocyte type. They are involved in regulating the body's immune response. The function of T helper cells generally is to mediate the immune response by secreting cytokines and interacting with B-cells to enhance or inhibit their activity. This is of particular importance in the gut as this is where the highest load of foreign material, food, is present.

Th3 cells are involved in mucosal immunity and protecting mucosal surfaces in the gut from non-pathogenic non-self antigens. They mediate this non-inflammatory environment by secreting TGF-β and IL-10. TGF-beta promotes the class switch to low concentrations of IgA which is noninflammatory. IgA does not usually activate the complement system and is not involved with phagocytosis. Th3 inhibits Th1 and Th2 cells.

Th3 cells 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),[1] 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 lineage 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,[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 cytotoxic T-lymphocyte antigen 4 (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.


  1. ^ Sakaguchi, S; Ono, M; Setoguchi, R; Yagi, H; Hori, S; Fehervari, Z; Shimizu, J; Takahashi, T; Nomura, T (2006). "Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease". Immunol Rev. 212: 8–27. doi:10.1111/j.0105-2896.2006.00427.x. PMID 16903903. 
  2. ^ Johansson, C; Kelsall, BL (2005). "Phenotype and function of intestinal dendritic cells". Semin Immunol. 17 (4): 284–294. doi:10.1016/j.smim.2005.05.010. PMID 15978836. 
  3. ^ Iwasaki, A (2007). "Mucosal dendritic cells". Annu Rev Immunol. 25: 381–418. doi:10.1146/annurev.immunol.25.022106.141634. PMID 17378762. 
  4. ^ Chen, W; Jin, W; Hardegen, N; Lei, KJ; Li, L; Marinos, N; McGrady, G; Wahl, SM (2003). "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. 198 (12): 1875–1886. doi:10.1084/jem.20030152. PMC 2194145Freely accessible. PMID 14676299.