The regulatory role of natural killer cells in multiple sclerosis

Brain : a Journal of Neurology
Kazuya TakahashiT Yamamura

Abstract

Multiple sclerosis is a chronic demyelinating disease of presumed autoimmune pathogenesis. The patients with multiple sclerosis typically shows alternating relapse and remission in the early stage of illness. We previously found that in the majority of multiple sclerosis patients in a state of remission, natural killer (NK) cells contain unusually high frequencies of the cells expressing CD95 (Fas) on their surface (>36.0%). Here we report that in such 'CD95+ NK-high' patients, NK cells may actively suppress potentially pathogenic autoimmune T cells that can mediate the inflammatory responses in the CNS. Using peripheral blood mononuclear cells (PBMCs) derived from 'CD95+ NK-high' or 'CD95+ NK-low' multiple sclerosis in a state of remission, we studied the effect of NK cell depletion on the memory T cell response to myelin basic protein (MBP), a major target antigen of multiple sclerosis. When we stimulated PBMCs of the 'CD95+ NK-high' multiple sclerosis after depleting CD56+ NK cells, a significant proportion of CD4+ T cells (1/2000 to 1/200) responded rapidly to MBP by secreting interferon (IFN)-gamma, whereas such a rapid T cell response to MBP could not be detected in the presence of NK cells. Nor did we detect the memory r...Continue Reading

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