Eur J Immunol 2002 Nov;32(11):3216-24
Mendel I, Shevach EM.
Laboratory of Immunology, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, USA.
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.