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.
Dandekar
Ajai A
AA
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Jacobsen
Gary
G
Waldschmidt
Thomas J
TJ
Perlman
Stanley
S
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