Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells

Int Immunopharmacol. 2009 May;9(5):540-5. doi: 10.1016/j.intimp.2009.01.022. Epub 2009 Jan 31.

Abstract

Naïve antigen-specific CD4(+) T cells (TxA23) induce autoimmune gastritis when transferred into BALB/c nu/nu mice. Transfer of in vitro pre-differentiated Th1 or Th17 TxA23 effector T cells into BALB/c nu/nu recipients induces distinct histological patterns of disease. We have previously shown that co-transfer of polyclonal naturally occurring Treg (nTreg) suppressed development of Th1-, but not Th17-mediated disease. Therefore, we analysed the suppressive capacity of different types of Treg to suppress Th1- and Th17-mediated autoimmune gastritis. We compared nTreg with polyclonal TGFbeta-induced WT Treg (iTreg) or TGFbeta-induced antigen-specific TxA23 iTreg in co-transfer experiments with Th1 or Th17 TxA23 effector T cells. 6 weeks after transfer in vitro pre-differentiated TxA23 Th1 and Th17 effector cells induced destructive gastritis. Th1-mediated disease was prevented by co-transfer of nTreg and also antigen-specific iTreg, whereas WT iTreg did not show an effect. However, Th17-mediated disease was only suppressed by antigen-specific iTreg. Pre-activation of nTreg in vitro prior to transfer did not increase their suppressive activity in Th17-mediated gastritis. Thus, antigen-specific iTreg are potent suppressors of autoimmune gastritis induced by both, fully differentiated Th1 and Th17 effector cells.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Cell Differentiation
  • Gastritis / immunology*
  • Gastritis / pathology
  • Immune Tolerance
  • Interleukin-17 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Stomach / pathology
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Thymus Gland / pathology
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens
  • Interleukin-17
  • Transforming Growth Factor beta