The IL-10-producing competence of Th2 cells generated in vitro is IL-4 dependent

Eur J Immunol. 2002 Nov;32(11):3216-24. doi: 10.1002/1521-4141(200211)32:11<3216::AID-IMMU3216>3.0.CO;2-H.

Abstract

Previous studies have suggested that activation of CD4+ T cells in the presence of IL-10 results in the generation of a population of T cells, T regulatory 1 (Tr1) cells, that primarily produce IL-10 and TGF-beta, but not IL-4. The relationship between Tr1 cells and conventional Th2 cells remains unclear. We were not successful in our attempts to generate significant numbers of antigen-specific T cells that secreted IL-10, but not IL-4, by culture in the presence of IL-10. The small numbers of cells that produced IL-10 only were completely dependent on the presence of IL-4 for their generation. In a polyclonal model, the development of IL-10 only producers was completely dependent on the presence of signal transducer and activator of transcription 6. Studies with myelin basic protein-specific T cells derived from an IL-4-deficient mouse confirmed the absolute requirement for IL-4 for the generation of IL-10 producers under all culture conditions. These IL-10-producing Th2 cells failed to inhibit EAE in an adoptive transfer model and were pathogenic when transferred to immunodeficient mice. Collectively, our results raise doubts about the existence of a unique population of CD4+ regulatory T cells that can be generated by activation in the presence of IL-10.

MeSH terms

  • Animals
  • DNA-Binding Proteins / physiology
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis*
  • Interleukin-4 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • STAT6 Transcription Factor
  • Th1 Cells / physiology
  • Th2 Cells / immunology*
  • Trans-Activators / physiology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • V(D)J recombination activating protein 2
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma