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KMID : 0381120080300040399
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Genes and Genomics
2008 Volume.30 No. 4 p.399 ~ p.405
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Vitamin D3 and Dexamethasone Induce Type I Regulatory T Cells That Confer Their Immunosuppressive Functions Via IL10 and CTLA4 Molecules
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Yun Dae-Sun
Gi Mi-A
Hong Seok-Mann
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Abstract
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Type 1 regulatory T (Tr1) cells play an important role in maintaining peripheral tolerance. Upon stimulation through TCR, Tr1 cells produce IL10 but not IL4 nor IFNγ, which are distinct from Th2 or Th1 subpopulations. The molecular mechanisms by which Tr1 cells regulate immune responses are not well understood. To investigate the phenotype and functions of Tr1 cells, we generated Tr1 cells in vitro by culturing naive CD4+ T cells from ovalbumin-specific TCR transgenic (OTII) mice with the immunosuppressive drugs vitamin D3 (VitD3) and dexamethasone (Dex). The VitD3/Dex-induced Tr1 cells from OTII mice could produce a large amount of IL10 but not IL4 nor IFNγ and express higher levels of CTLA4 than control group. We also demonstrated the immunosuppressive effect of VitD3/Dex-induced Tr1 cells on the proliferation of CFSE-labeled naive CD4+ T cells stimulated with anti-CD3/anti-CD28 mAbs. Furthermore, the transwell assay and antibody blocking experiments demonstrated that the inhibitory effect of these cells is mediated by CTLA4 as well as IL10. Our findings show for the first time that Tr1 cells confer their immunosuppressive functions via CTLA4 molecules. Taken together, the IL10-producing Tr1 cells might be one of the valuable candidates to immunotherapy for autoimmune diseases.
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KEYWORD
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vitamin D3, Dexamethasone, type I regulatory T cells, interleukin 10, CTLA4
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