Analysis of TGF-ß1 and TGF-ß3 as regulators of encephalitogenic Th17 cells: Implications for multiple sclerosis.

ABSTRACT

The phenotype of the CD4(+) T cells that mediate the CNS pathology in multiple sclerosis is still unclear, and yet a vital question for developing therapies. One of the conundrums is the role of TGF-ß in the development of encephalitogenic Th17 cells. In the present study, TGF-ß1 and TGF-ß3 were directly compared in their capacity to promote the differentiation of myelin-specific Th17 cells that could induce experimental autoimmune encephalomyelitis (EAE). Myelin-specific CD4(+) T cell receptor transgenic cells differentiated with antigen in the presence of IL-6+TGF-ß1 or IL-6+TGF-ß3 generated T cells that produced robust amounts of IL-17, but were incapable of inducing EAE when transferred into mice. Further analysis of these non-encephalitogenic Th17 cells found that they expressed lower amounts of GM-CSF or IL-23R, both molecules necessary for encephalitogenicity. Thus, TGF-ß, irrespective of isoform, negatively regulates the differentiation of encephalitogenic Th17 cells.