The IL-10-producing competence of Th2 cells generated in vitro is IL-4 dependent.
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.
Mendel
Itzhak
I
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
Shevach
Ethan M
EM
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma