Multiple sclerosis and immune regulatory cells.

Abstract

The multiple sclerosis disease process is defined on the basis of lesions disseminated in space and time within the CNS. Immunization of humans (vaccines) and animals with neural tissue can result in multi-focal CNS inflammatory lesions with demyelination; such disorders are usually uniphasic or self-limited. They are initiated by systemically activated myelin-reactive T cells that then access the CNS. Myelin-reactive T cells can be recovered from the CNS and blood in multiple sclerosis. Such cells can also be recovered from unaffected individuals. These observations raise issues regarding the origin of such cells in non-immunized individuals and why their presence is variably associated with uniphasic disease, recurrent disease, or no disease. Most autoreactive cells may actually be generated in response to exogenous peptide antigens with which there is cross-reactivity (molecular mimicry) with myelin antigens, reflecting the degeneracy of antigen recognition by T-cell receptors (Nino-Vasquez et al ., 2004). Studies in animals showing that depletion of specific subpopulations of immune cells can unmask spontaneous or antigen-induced autoimmune disease, or conversely that such cells can transfer disease resistance, indicate that active immune-regulatory mechanisms contribute to the disconnection between the presence of autoreactive T cells and the development of autoimmune disease. As the capacity to define subsets of immune …