? ECDI-coupled cell tolerance renders CD4+ T cells unresponsive to antigen-specific stimulation and has been used to inhibit and to prevent several animal models of autoimmune disorders. Preliminary data indicates that the same method used to tolerize CD4+ T cells renders CD8+ T cells unresponsive to subsequent stimulation as well. This treatment dramatically reduced CD8+ T cell effector function as well as altered viral clearance and susceptibility to demyelinating disease in mice infected with Theiler's murine encephalomyelitis virus (TMEV), a model of human multiple sclerosis. The tolerance of CD8+ T cells has potential applications for both the study of specific populations of cells in various infections and diseases as well as potential for immuno-therapy in autoimmune diseases in which CD8+ T cells mediate damage. Therefore, it is essential that the mechanisms of tolerance of CD8+ T cells be elucidated. The overall goal of this research proposal is to explore the functions of CD8+ T cells and the effects that ECDI-coupled cell tolerance has on their roles in both viral clearance and CD8+ T cell-mediated CNS autoimmune disease. ? ?
| Richards, Maureen H; Getts, Meghann Teague; Podojil, Joseph R et al. (2011) Virus expanded regulatory T cells control disease severity in the Theiler's virus mouse model of MS. J Autoimmun 36:142-54 |
| Getts, Meghann Teague; Richards, Maureen H; Miller, Stephen D (2010) A critical role for virus-specific CD8(+) CTLs in protection from Theiler's virus-induced demyelination in disease-susceptible SJL mice. Virology 402:102-11 |
| Getts, Meghann Teague; Kim, Byung S; Miller, Stephen D (2007) Differential outcome of tolerance induction in naive versus activated Theiler's virus epitope-specific CD8+ cytotoxic T cells. J Virol 81:6584-93 |
