CNS-Specific, Autoreactive CD8+ T Cells Have a Regulatory Role in Autoimmune Demyelination

Multiple Sclerosis (MS) is an inflammatory disorder characterized by the destruction of myelin sheaths, which encase neurons of the central nervous system. A great deal of our current knowledge about the immune pathogenesis of MS derives from work in its murine model, experimental autoimmune encephalomyelitis (EAE), which can be induced by inoculation with a specific neuroantigen or by adoptive transfer of CNS-specific activated T cells. The vast majority of studies in MS and EAE have focused on the role of CD4+ T cells in this disease, with the underlying assumption that MS, like EAE, is a CD4+ Th1-mediated autoimmune disease. However, several reports have implicated both CD4+ and CD8+ T cells in the pathogenesis and regulation of these diseases. In this study, we show the presence of antigen-specific, autoreactive CD8+ T cells in several models of EAE. Furthermore, through series of adoptive transfer studies, we show that these cells play a regulatory role in the pathogenesis of autoimmune demyelination. Using novel in vivo killing assays, we show that these cells retain their killing capacity and that they target both activated APC and CD4+ T cells that have been loaded with the specific antigen. These cells are also shown to produce cytokines that may be involved in disease regulation. We also show that these cells modify antigen-presenting capacity of APC. In conclusion, our studies provide strong evidence that antigen-specific CD8+ T cells are involved in regulatory processes in the context of autoimmune demyelination