Cutting edge: antigen-specific TGF beta-induced regulatory T cells suppress Th17-mediated autoimmune disease

J Immunol. 2008 Dec 15;181(12):8209-13. doi: 10.4049/jimmunol.181.12.8209.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / prevention & control*
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Gastritis / immunology*
  • Gastritis / prevention & control*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, Transgenic
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / transplantation
  • Transforming Growth Factor beta / physiology*

Substances

  • Epitopes, T-Lymphocyte
  • Interleukin-17
  • Transforming Growth Factor beta