Opposing T cell responses in experimental autoimmune encephalomyelitis

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. Activated clonally expanded CD4 + T cells display specificity to the myelin peptide MOG, whereas clonally expanded CD8 + T cells depend on T cell receptor recognition of unrelated surrogate peptides and have a regulatory function.