TY - JOUR
T1 - Coexpression of Class I Major Histocompatibility Antigen and Viral RNA in Central Nervous System of Mice Infected With Theiler's Virus
T2 - A Model for Multiple Sclerosis
AU - LINDSLEY, MARK D.
AU - PATICK, AMY K.
AU - PRAYOONWIWAT, NARAPORN
AU - RODRIGUEZ, MOSES
N1 - Funding Information:
This study was supported in part by Research Grants NS 24180 from the National Institutes of Health, Public Health Service, and RG 1878 and RG 2174 from the National Multiple Sclerosis Society.
PY - 1992
Y1 - 1992
N2 - Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class IMHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in “upregulation” of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.
AB - Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class IMHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in “upregulation” of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.
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U2 - 10.1016/S0025-6196(12)60820-9
DO - 10.1016/S0025-6196(12)60820-9
M3 - Article
C2 - 1434926
AN - SCOPUS:0026759330
SN - 0025-6196
VL - 67
SP - 829
EP - 838
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 9
ER -