CHARACTERIZATION OF AND FUNCTIONAL ANTIGEN PRESENTATION BY CENTRAL-NERVOUS-SYSTEM MONONUCLEAR-CELLS FROM MICE INFECTED WITH THEILERS MURINEENCEPHALOMYELITIS VIRUS

We examined the phenotype and function of cells infiltrating the centr al nervous system (CNS) of mice persistently infected with Theiler's m urine encephalomyelitis virus (TMEV) for evidence that viral antigens are presented to T cells within the CNS. Expression of major histocomp atibility complex (MHC) class II in the spinal cords of mice infected with TMEV was found predominantly on macrophages in demyelinating lesi ons. The distribution of I-A(s) staining overlapped that of the macrop hage marker sialoadhesin in frozen sections and coincided with that of another macrophage/microglial cell marker, F4/80, by flow cytometry. In contrast, astrocytes, identified by staining with glial fibrillary acidic protein, rarely expressed detectable MHC class II, although fib rillary gliosis associated with the CNS damage was clearly seen. The c ostimulatory molecules B7-1 and B7-2 were expressed on the surface of most MHC class II-positive cells in the CNS, at levels exceeding those found in the spleens of the infected mice. Immunohistochemistry revea led that B7-1 and B7-2 colocalized on large F4/80(+) macrophages/micro glia in the spinal cord lesions. In contrast, CD4(+) T cells in the le sions expressed mainly B7-2, which was found primarily on blastoid CD4 + T cells located toward the periphery of the lesions. Most interestin gly, plastic-adherent cells freshly isolated from the spinal cords of TMEV-infected mice were able to process and present TMEV and horse myo globin to antigen-specific T-cell lines. Furthermore, these cells were able to activate a TMEV epitope-specific T-cell line in the absence o f added antigen, providing conclusive evidence for the endogenous proc essing and presentation of virus epitopes within the CNS of persistent ly infected SJL/J mice.