A critical role for virus-specific CD8(+) CTLs in protection from Theiler's virus-induced demyelination in disease-susceptible SJL mice.
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a relevant mouse model of multiple sclerosis. Infection of susceptible SJL/J mice leads to life-long CNS virus persistence and development of a chronic T cell-mediated autoimmune demyelinating disease triggered via epitope spreading to endogenous myelin epitopes. Potent CNS-infiltrating CD8(+) T cell responses to TMEV epitopes have previously been shown to be induced in both disease-susceptible SJL/J and resistant C57BL/6 mice, in which the virus is rapidly cleared. Specific tolerization of SJL CD8(+) T cells specific for the immunodominant TMEV VP3(159)(-)(166) epitope has no effect on viral load or development of clinical TMEV-IDD, but adoptive transfer of activated CD8(+) VP3(159)(-)(166)-specific T cell blasts shortly after TMEV infection to boost the early anti-viral response leads to clearance of CNS virus and protection from subsequent TMEV-IDD. These studies have important implications for vaccine strategies and treatment of chronic infections in humans.
Getts
Meghann Teague
MT
Department of Microbiology and Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303, E. Chicago Ave., Chicago, IL 60611, USA.
Richards
Maureen H
MH
Miller
Stephen D
SD
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D003711:Demyelinating Diseases / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte
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