Regulatory T cells in the control of inflammatory demyelinating diseases of the central nervous system

Abstract

New concepts in fundamental immunology, in particular the identification of a lineage of CD4 T cells endowed with regulatory properties, have revolutionized the understanding of immune-mediated diseases both in experimental models and in humans. The impact of the T regulatory cells, characterized by the expression of CD25 and the foxp3 transcription factor, on the development and remission from central nervous system inflammation, and their therapeutic potential, is being aggressively studied in preclinical animal models. Recent data indicate that the CD4CD25foxp3 T regulatory cells act both at the level of secondary lymphoid organs and in the inflamed central nervous system during experimental autoimmune encephalomyelitis. They contribute to the natural protection against autoimmunity and participate in the spontaneous remission of disease. Their role in multiple sclerosis is still unclear, but convergent data indicate that circulating CD4CD25 T cells from patients with multiple sclerosis exhibit defective regulatory properties. Several disease-modifying therapies act on T regulatory cells and their beneficial effects on multiple sclerosis could, in part, result from this mode of action. A better understanding of the induction of T regulatory cells, of their mechanisms of action, and of approaches to manipulate them in vivo may offer new therapeutic opportunities for patients with multiple sclerosis.