Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination.
C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a clinically evident, demyelinating encephalomyelitis. Infectious virus can be isolated from the spinal cords of these mice and is invariably mutated in the immunodominant CD8 T-cell epitope recognized in this strain. We showed previously that these persistently infected mice did not mount a measurable serum anti-MHV neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL) escape was not detected in MHV-infected BALB/b mice (H-2(b) haplotype), even though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice had 25-fold more MHV-specific antibody-secreting cells in the central nervous system, the site of infection, than B6 mice, suggesting that local production of anti-MHV antibody contributed to this absence of CTL escape. Additionally, administration of anti-MHV neutralizing antibody to infected B6 mice suppressed the development of CTL escape mutants. These findings indicate a key role for the anti-MHV antibody response in suppressing virus replication, thereby minimizing the emergence and competitive advantage of CTL escape mutants.
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Ajai A
AA
Dandekar
Gary
G
Jacobsen
Thomas J
TJ
Waldschmidt
Stanley
S
Perlman
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000914:Antibodies, Viral