The role of CD4 T cells in the pathogenesis of multiple sclerosis.

T lymphocytes play a central role in the pathogenesis of multiple sclerosis (MS) (Zhang et al., 1992). Both CD4+ and CD8+ T cells have been demonstrated in MS lesions, with CD4+ T cells predominating in acute lesions and CD8+ T cells being observed more frequently in chronic lesions (Raine, 1994). Additionally, T cells are found in all four of the described histopathologic subtypes of MS (Lucchinetti et al., 2000). Activated myelin-reactive CD4+ T cells are present in the blood and cerebrospinal fluid (CSF) of MS patients; in contrast, only nonactivated myelin-reactive T cells are present in the blood of controls (Zhang et al., 1994). The success of several T-cell-targeted therapies in MS reinforces the importance of the role of the T cell in MS pathogenesis. Here, we outline basic concepts in CD4+ T-cell immunology and summarize the current understanding of the role of CD4+ T cells in the pathogenesis of MS.