Rapid in vivo conversion of effector T cells into Th2 cells during helminth infection

J Immunol. 2012 Jan 15;188(2):615-23. doi: 10.4049/jimmunol.1101164. Epub 2011 Dec 7.

Abstract

Stimulation of the immune system by pathogens, allergens, or autoantigens leads to differentiation of CD4(+) T cells with pro- or anti-inflammatory effector cell functions. Based on functional properties and expression of characteristic cytokines and transcription factors, effector CD4(+) T cells have been grouped mainly into Th1, Th2, Th17, and regulatory T (Treg) cells. At least some of these T cell subsets remain responsive to external cues and acquire properties of other subsets, raising the hope that this functional plasticity might be exploited for therapeutic purposes. In this study, we used an Ag-specific adoptive transfer model and determined whether in vitro-polarized or ex vivo-isolated Th1, Th17, or Treg cells can be converted into IL-4-expressing Th2 cells in vivo by infection of mice with the gastrointestinal helminth Nippostrongylus brasiliensis. Th1 and Th17 cells could be repolarized to acquire the expression of IL-4 and lose the expression of their characteristic cytokines IFN-γ and IL-17A, respectively. In contrast, both in vitro-generated and ex vivo-isolated Treg cells were largely resistant to repolarization. The helminth-induced conversion of Th1 or Th17 cells into Th2 cells may partially explain the inverse correlation between helminth infection and protection against autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Polarity / genetics
  • Cell Polarity / immunology
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Nippostrongylus / immunology
  • Strongylida Infections / immunology*
  • Strongylida Infections / metabolism
  • Strongylida Infections / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / parasitology
  • T-Lymphocytes, Regulatory / transplantation
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Th1 Cells / transplantation
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Th17 Cells / transplantation
  • Th2 Cells / immunology*
  • Th2 Cells / parasitology
  • Th2 Cells / pathology

Substances

  • Epitopes, T-Lymphocyte
  • Interleukin-4
  • Interferon-gamma