Early T cell response in the central nervous system in canine distemper virus infection

The initial demyelinating lesions in canine distemper virus (CDV) infection develop during a period of severe immunosuppression in the absence of infl ammation. In vitro and in vivo studies suggest that early demyelination is due to directly virus-induced oligodendroglial changes. In the present spat iotemporal study in experimentally CDV-infected dogs we observed diffuse up -regulation of T cells throughout the central nervous system (CNS) and T ce ll invasion in early demyelinating lesions. Invasion of T cells in the CNS occurred despite severe immunosuppression and without any perivascular cuff ing. However, the major fraction of invading T cells correlated with sites of viral replication and coincided with the demonstration of an early immun e response against the nucleocapsid protein of CDV. Activation of microglia l cells was thought to have elicited the migration of T cells to the CNS by secretion of chemokines: marked IL-8 activity was found in the CSF of dogs with acute lesions. In areas of early demyelination, large numbers of CD3( +) cells accumulated in the tissue in the absence of any morphological sign of inflammation. Whether the T cells at lesion sites contribute to the dev elopment of acute demyelination remains uncertain at this stage. Antiviral cytotoxicity was not apparent since viral clearance in demyelinating lesion s is only effective when B cells and concurring antiviral antibody producti on appeared in the subacute and chronic inflammatory stage of the disease. CD3(+) cells appear to persist for several weeks after infection since they were also found in recovered dogs that did not develop demyelination. Accu mulation of immune cells, including a significant proportion of resting T c ells (CD45RA(+)) in the CNS in the early stages of the disease may facilita te the later development of the intrathecal immune response and associated immunopathological complications.