Faculty Collaboration Database

CD4(+) and CD8(+) T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis. J Virol 1998 Sep;72(9):7320-9

Date

08/08/1998

Pubmed ID

9696828

Pubmed Central ID

PMC109956

DOI

10.1128/JVI.72.9.7320-7329.1998

Scopus ID

2-s2.0-0031821271 (requires institutional sign-in at Scopus site)   110 Citations

Abstract

Following intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), susceptible strains of mice (SJL and PLJ) develop virus persistence and demyelination similar to that found in human multiple sclerosis. Resistant strains of mice (C57BL/6) clear virus and do not develop demyelination. To resolve the controversy about the role of CD4(+) and CD8(+) T cells in the development of demyelination and neurologic deficits in diseases of the central nervous system, we analyzed TMEV infection in CD4- and CD8-deficient B6, PLJ, and SJL mice. Genetic deletion of either CD4 or CD8 from resistant B6 mice resulted in viral persistence and demyelination during the chronic stage of disease. Viral persistence and demyelination were detected in all strains of susceptible background. Although genetic deletion of CD8 had no effect on the extent of demyelination in susceptible strains, deletion of CD4 dramatically increased the degree of demyelination observed. Whereas strains with deletions of CD4 showed severe neurologic deficits, mice with deletions of CD8 showed minimal or no deficits despite demyelination. In all strains, deletion of CD4 but not CD8 resulted in a decreased delayed-type hypersensitivity response to viral antigen. We conclude that each T-cell subset makes a discrete and nonredundant contribution to protection from viral persistence and demyelination in resistant strains. In contrast, in susceptible strains, CD8(+) T cells do not provide protection against chronic demyelinating disease. Furthermore, in persistent TMEV infection of the central nervous system, neurologic deficits appear to result either from the absence of a protective class II-restricted immune response or from the presence of a pathogenic class I-restricted response.

Author List

Murray PD, Pavelko KD, Leibowitz J, Lin X, Rodriguez M

Author

Paul D. Harker-Murray MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Viral
Antigens, Viral
Brain
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Causality
Demyelinating Diseases
Disease Susceptibility
Female
Genotype
Hypersensitivity, Delayed
Male
Mice
Mice, Inbred C57BL
Multiple Sclerosis
Poliomyelitis
Theilovirus
Virus Latency