Immune-mediated mechanisms of resistance to TMEV-induced demyelinating disease in BALB/cByJ mice

Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which can induce CNS demyelination in mice and has been studied as an animal model of MS. The BALB/cByJ is genetically resistant to TMEV-IDD. However, pretreatment with low dose irradiation can convert these resistant mice to a susceptible phenotype. Adoptively transferred CD8+ T cells, but not CD4+ T cells, from infected, unirradiated C/cByJ donors can restore resistance to irradiatated, infected C/cByJ mice suggesting a "protective" role for the CD8+ T cell population. We have developed an in vivo system in which to investigate the possible regulatory ability of CD8+ T cells from infected, resistant C/cByJ mice on TMEV-specific T cell blasts. Recipients of these TMEV-specific blasts generated significantly higher TMEV-specific DTH and T cell proliferation as compared to those mice that did not receive blasts. Since these TMEV-specific T cell blasts have the ability to accelerate TMEV-IDD, it was determined whether co-transferring these blasts with "protective" CD8+ T cells from infected, resistant C/cByJ donors changed their potentiating ability. We have demonstrated that CD8+ T cells from infected, resistant C/cByJ have in vivo regulatory function and irradiation appears to alter this function.