Exploring the roles of CD8(+) T lymphocytes in the pathogenesis of autoimmune demyelination

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by mononuclear cell infiltrates, focal demyelination, and the development of sclerotic plaques within the central nervous system. Although CD8(+) T lymphocytes are more abundant than CD4(+) T lymphocytes in MS lesions, the latter cell type has been most commonly implicated in the genesis of this disease. Recent evidence, however, suggests that both T cell populations and their various subsets are able to contribute to disease initiation and progression. To gain insight into disease mechanisms of potential relevance to MS, a variety of animal models have been developed. Foremost among these has been experimental autoimmune encephalomyelitis (EAE), a rodent model of MS induced by the immunization of genetically susceptible animals with peptides derived from myelin-associated proteins. While EAE has contributed greatly to our understanding of mechanisms involved in autoimmune demyelination, this model has been of limited use as far as shedding light on the possible contributions of CD8(+) T lymphocytes to disease pathogenesis. Herein, we review evidence supporting a role for CD8(+) T lymphocytes in both MS and EAE and also highlight several novel murine systems designed for investigating the role(s) of CD8(+) T cells in autoimmune demyelination.