Opposing T cell responses in experimental autoimmune encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis is a model for multiple sclerosis. Here we show that induction generates successive waves of clonally expanded CD4⁺, CD8⁺ and γδ⁺ T cells in the blood and central nervous system, similar to gluten-challenge studies of patients with coeliac disease. We also find major expansions of CD8⁺ T cells in patients with multiple sclerosis. In autoimmune encephalomyelitis, we find that most expanded CD4⁺ T cells are specific for the inducing myelin peptide MOG_35–55. By contrast, surrogate peptides derived from a yeast peptide major histocompatibility complex library of some of the clonally expanded CD8⁺ T cells inhibit disease by suppressing the proliferation of MOG-specific CD4⁺ T cells. These results suggest that the induction of autoreactive CD4⁺ T cells triggers an opposing mobilization of regulatory CD8⁺ T cells.