Experimental autoimmune encephalomyelitis is a model for multiple sclerosis. Here we show that induction generates successive waves of clonally expanded CD4(+), CD8(+) and gamma delta(+) 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.