T-Cells in Multiple Sclerosis

Christopher Severson, David A. Hafler

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system pathologically characterized by lesions of infiltrating macrophages and T cells. Multiple lines of evidence implicate that T cells play a central role in both mediating and regulating MS pathophysiology, and efforts to develop rational therapeutic strategies for MS have focused on understanding factors which control T cell function. T cells are a highly heterogeneous population comprised of multiple cell subtypes which mediate both adaptive immunity and specific tolerance. Much has been learned about the molecular signals that induce T cell activation and differentiation, and several effective treatments for MS act by altering these activation and differentiation pathways. In recent years, increasing recognition has been given to T cell subsets which serve immunosuppressive or regulatory functions, and it has been discovered that patients with MS have a functional defect in these cells. Current work is beginning to shed light on interactions of pathogenic and regulatory T cells with the intrinsic cells of the CNS to provide a more comprehensive picture of MS pathogenesis.