Absence of spontaneous central nervous system remyelination in class II-deficient mice infected with Theiler's virus

We previously showed that Theiler's murine encephalomyelitis virus (TMEV)-i nfected major histocompatibility complex (MHC) class II-deficient mice deve lop both demyelination and neurologic deficits, whereas MHC class I-deficie nt mice develop demyelination but no neurologic deficits. The absence of ne urologic deficits in the class I-deficient mice was associated with preserv ed sodium channel densities in demyelinated lesions, a relative preservatio n of axons, and extensive spontaneous remyelination. In this study, we inve stigated whether TMEV-infected class II-deficient mice, which have an ident ical genetic background (C57BL/6 x 129) as the class I-deficient mice, have preserved axons and spontaneous myelin repair following,a chronic TMEV-inf ection. Both class I- and class II-deficient mice showed similar extents of demyelination of the spinal cord white matter 4 months after TMEV infectio n. However, the class I-deficient mice demonstrated remyelination by oligod endrocytes, whereas class II-deficient mice showed minimal if any myelin re pair. Demyelinated lesions, characterized by inflammatory infiltrates in bo th mutants, revealed disruption of axons in class II- but not class I-defic ient mice. Further characterization revealed that even though class II-defi cient mice lacked TMEV-specific IgG, they had virus-specific IgM, which, ho wever, did not neutralize TMEV in vitro. In addition, class II-deficient mi ce developed TMEV-specific cytotoxic T-lymphocytes in the CNS during the ac ute (7 days) disease, but these cytotoxic lymphocytes were not present in t he chronic stage of disease, despite a high titer of infectious virus throu ghout the disease. We envision that the presence of demyelination, high vir us titer, absence of remyelination, and axonal disruption in chronically in fected class II-deficient mice contributes to the development of paralytic disease.