UP-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN EXPRESSION IN THE CENTRAL-NERVOUS-SYSTEM OF DOGS WITH SPONTANEOUS CANINE-DISTEMPER VIRUS ENCEPHALITIS

Major histocompatibility complex class II (MHC II) and canine distempe r virus (CDV) antigen expression were compared by immunohistochemistry in the cerebellar white matter of ten dogs with naturally occurring c anine distemper encephalitis. In addition, infiltrating mononuclear ce lls were characterized by employing poly- and monoclonal antibodies di rected against human CD3, canine MHC II, CD5, B cell antigen and CDV-s pecific nucleoprotein. Positive antigen-antibody reaction was visualiz ed by the avidin-biotin-peroxidase complex method on frozen sections. Histologically, neuropathological changes were categorized into acute, subacute, and chronic. In control brains, MHC II expression was weak and predominantly detected on resident microglia of the white matter a nd on endothelial, perivascular and intravascular cells. In CDV antige n-positive brains, MHC II was mainly found on microglia and to a lesse r extent on endothelial, meningeal, choroid plexus epithelial, ependym al and intravascular cells. In addition, virtually all of the perivasc ular cells expressed MHC II antigen. CDV antigen was demonstrated most frequently in astrocytes. Of the perivascular lymphocytes, the majori ty were CD3-positive cells, followed by B cells. Only a small proporti on of perivascular cells expressed the CD5 antigen. In addition, B cel ls and CD3 and CD5 antigen-positive cells were found occasionally in s ubacute and frequently in chronic demyelinating plaques. In acute ence phalitis, CDV antigen exhibited a multifocal or diffuse distribution, and MHC II was moderately up-regulated throughout the white matter and accentuated in CDV antigen-positive plaques. In subacute encephalitis , moderate multifocal CDV antigen and moderate to strong diffuse MHC I I-specific staining, especially prominent in CDV antigen-positive lesi ons, were observed. In chronic encephalitis, CDV antigen expression wa s restricted to single astrocytes at the edge of the lesions or was ab sent, while MHC II expression, especially prominent on microglia, was strongly upregulated throughout the white matter, most pronounced in d emyelinated plaques. In summary, in acute and subacute lesions without perivascular cuffs, MHC II expression correlated with the presence of CDV antigen. In contrast, in chronic lesions, MHC II expression on mi croglial cells was the most prominent despite a few CDV antigen-positi ve astrocytes, indicating that nonviral antigens may play an important role as triggering molecules for the process of demyelination.