[Immune tolerance and control of CNS autoimmunity: from animal models to MS patients]. / Tolérance immunitaire vis-à-vis d'auto-antigènes du système nerveux: implications thérapeutiques.

ABSTRACT

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease resulting in demyelination and axonal loss within the central nervous system (CNS). An autoimmune reaction directed against CNS antigens contributes to the disease process. Since the CNS has long been considered as an immune privileged site, how such an immune response can develop locally has remained enigmatic. Recent data, mostly based on the study of animal models for MS, have shown that the CNS is in fact more permissive to the development of immune responses than previously thought. This observation is counterbalanced by the fact that immune tolerance to neural antigens can be induced outside the CNS. This review focuses on the mechanisms preventing CNS autoimmunity, which act in three separate tissues. STATE OF THE ART In the thymus, expression of CNS auto-antigens promotes partial protection, notably through elimination of autoreactive T cells. In the secondary lymphoid organs, the remaining autoreactive T cells are kept under control by the thymus-derived naturally occurring regulatory T cells of the CD4(+) Foxp3(+) phenotype. In the CNS, multiple mechanisms including the local activation of regulatory T cells further limit autoimmunity. CONCLUSIONS AND PERSPECTIVES A better understanding of the induction of regulatory T cells, of their mechanisms of action, and of approaches to manipulate them in vivo may offer new therapeutic opportunities for MS patients.