V(beta)8(+) T cells protect from demyelinating disease in a viral model of multiple sclerosis.
Previous studies illustrated the influence of T cell subsets on susceptibility or resistance to demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. Genetic segregation analysis showed a correlation with disease phenotype in this model with particular V(beta) genes. In this study we investigated the contribution of specific V(beta) TCR to the pathogenesis of virus-induced demyelinating disease. Spectratype analysis of cells infiltrating the CNS early in infection demonstrated an over-representation of V(beta)8(+) T cells in mice expressing a susceptible H-2 haplotype. We infected transgenic mice expressing the V(beta)8.2 TCR directed against a non-TMEV antigen and found an increase in demyelinating disease in mice of either susceptible or resistant background compared with littermate controls. In addition, depletion studies with an anti-V(beta)8-specific antibody in both susceptible (B10.Q) and resistant (C57BL/6) mice resulted in increased demyelination. TCR analysis of VP2-specific cytotoxic T cell clones from mice with a resistant genotype identified only the V(beta)8.1 TCR, suggesting that limited T cell diversity is critical to TMEV clearance. Together, these results support a protective role for V(beta)8(+) T cells in virus-induced demyelinating disease.
Drescher
K M
KM
Departments of Neurology and Immunology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Johnston
S L
SL
Hogancamp
W
W
Nabozny
G H
GH
David
C S
CS
Rimm
I J
IJ
Wettstein
P J
PJ
Rodriguez
M
M
D000818:Animals; D001921:Brain / Q000473:pathology; D018188:Cardiovirus Infections / Q000276:immunology* / Q000473:pathology; D003711:Demyelinating Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000276:immunology; D007113:Immunity, Innate; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology*; D011051:Poliomyelitis / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017945:Theilovirus; D019076:Transgenes
D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta