Interleukin 17 production in central nervous system infiltrating T cells and glial cells is associated with active disease in multiple sclerosis.
Recent findings in the animal model for multiple sclerosis (MS) experimental autoimmune encephalomyelitis, implicate a novel CD4+ T cell subset (TH17) characterized by the secretion of interleukin 17 (IL 17) in disease pathogenesis. To elucidate its role in MS, brain tissues from patients with MS were compared to controls. We detected expression of IL 17 mRNA (by in situ hybridization) and protein (by immunohistochemistry) in perivascular lymphocytes as well as in astrocytes and oligodendrocytes located in the active areas of MS lesions. Further, we found a significant increase in the number of IL 17+ T cells in active rather than inactive areas of MS lesions. Specifically, double immunofluorescence showed that IL 17 immunoreactivity was detected in 79% of T cells in acute lesions, 73% in active areas of chronic active lesions, but in only 17% of those in inactive lesions and 7% in lymph node control tissue. CD8+ as well as CD4+ T cells were equally immunostained for IL 17 in MS tissues. Interestingly, and in contrast to lymph node T cells, no perivascular T cells showed FoxP3 expression, a marker of regulatory T cells, at any stage of MS lesions. These observations suggest an enrichment of both IL 17+CD4+ and CD8+ T cells in active MS lesions as well as an important role for IL 17 in MS pathogenesis, with some remarkable differences from the experimental autoimmune encephalomyelitis model.
The American journal of pathology