IFN-gamma production and astrocyte recognition by autoreactive T cells induced by Theiler's virus infection: role of viral strains and capsid proteins.

From mice infected with the DA strain of Theiler's murine encephalomyelitis virus (TMEV), CD8+ cytotoxic T lymphocytes (CTLs) could be detected after stimulation with TMEV infected antigen presenting cells (APCs). These CTLs killed not only TMEV infected but also uninfected syngeneic cells. Killing was associated with interferon (IFN)-gamma production in ELISPOT assays. The CTLs were efficiently induced by vaccinia virus encoding DA virus capsid proteins, but not by APCs infected with the GDVII strain of TMEV. The CTLs produced IFN-gamma in response to TMEV infected, but not uninfected, astrocytes. The CTLs could be maintained in the presence of interleukin (IL)-2. We hypothesized that, in DA virus infection, CD8+ CTLs specific for viral capsid protein could recognize self protein on oligodendrocytes by molecular mimicry, leading to demyelination.