Huter Eva N, Stummvoll Georg H, DiPaolo Richard J, Glass Deborah D, Shevach Ethan M
Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2008 Dec 15;181(12):8209-13. doi: 10.4049/jimmunol.181.12.8209.
CD4(+) T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase alpha-chain. When TxA23 CD4(+) thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by Th1 or Th2 cell lines could be prevented by the cotransfer of polyclonal Foxp3(+) T regulatory cells (nTreg), whereas Th17-induced AIG was resistant to suppression. We compared the capacity of different types of Treg to suppress Th17-mediated AIG. Cotransfer of either nTreg or polyclonal TGFbeta-induced Treg (iTreg) did not prevent AIG, while cotransfer of TGFbeta-induced Ag-specific TxA23 iTreg completely prevented the development of disease. Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed.
来自TCR转基因TxA23小鼠的CD4(+) T细胞识别H/K-ATP酶α链的一种肽段。当TxA23 CD4(+)胸腺细胞分化为Th1、Th2和Th17细胞系时，这三个亚群在转移至裸鼠受体后均诱导出自身免疫性胃炎（AIG）。幼稚T细胞或Th1或Th2细胞系诱导的AIG可通过共转移多克隆Foxp3(+) T调节细胞（nTreg）来预防，而Th17诱导的AIG对抑制具有抗性。我们比较了不同类型Treg抑制Th17介导的AIG的能力。共转移nTreg或多克隆TGFβ诱导的Treg（iTreg）均不能预防AIG，而共转移TGFβ诱导的抗原特异性TxA23 iTreg则完全预防了疾病的发展。抗原特异性iTreg在Th17效应细胞注射6天后注射能够抑制Th17介导的疾病。讨论了这些结果对于将Treg用于自身免疫性疾病细胞生物治疗的意义。
