Virus-induced autoimmunity: Epitope spreading to myelin autoepitopes in theiler's virus infection of the central nervous system

摘要: Epidemiological studies indicate that host immunogenetics and history of infection, particularly by viruses, may be a necessary cofactor for the induction variety autoimmune diseases. To date, however, there is no clear-cut evidence, either in experimental animal models or human disease, supports molecular mimicry (Wucherpfennig Strominger, 1995; Fujinami Oldstone, 1985) role superantigens (Scherer et al., 1993) initiation T cell-mediated autoimmunity. In contrast, current data provide compelling evidence support major epitope spreading myelin-specific autoimmunity mice persistently infected with TMEV. It significant two picornaviruses closely related to TMEV, coxsackievirus (Rose Hill, 1996) encephalomyocarditis virus (EMCV) (Kyu 1992), have been similarly shown persist (either viral RNA infectious virus) their target organs associated development chronic diseases, including myocarditis diabetes. Thus, inflammatory responses induced viruses trigger proinflammatory Th1 responses, ability genetically susceptible hosts, lead organ-specific disease via spreading. Epitope has important implications design antigen-specific therapies potential treatment MS other This process indicates diseases are evolving entities specificity effector autoantigen-specific cells varies during process. Our experiments employing tolerance R-EAE clearly ongoing possible preventing relapses, provided proper relapse-associated targeted (Vanderlugt 1999). However, identify epitopes humans will difficult task because immunodominance vary every individual. The use costimulatory antagonists can induce anergy without requiring prior knowledge exact (Miller 1995b), bystander suppression (Nicholson 1997; Brocke 1996), thus more practical alternative disease.