CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination

Gregory F Wu; Ajai A Dandekar; Lecia Pewe; Stanley Perlman

doi:10.4049/jimmunol.165.4.2278

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CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination

Journal article

Peer reviewed

CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination

Gregory F Wu, Ajai A Dandekar, Lecia Pewe and Stanley Perlman

Journal of immunology (Baltimore, Md. : 1950), Vol.165(4), pp.2278-2286

08/15/2000

DOI: 10.4049/jimmunol.165.4.2278

PMID: 10925317

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Abstract

A chronic demyelinating disease results from murine infection with the neurotropic strain JHM of mouse hepatitis virus (MHV-JHM). Demyelination is largely immune mediated. In this study, the individual roles of CD4 and CD8 T cells in MHV-induced demyelination were investigated using recombination-activating gene 1-/- (RAG1-/-) mice infected with an attenuated strain of MHV-JHM. These animals develop demyelination only after adoptive transfer of splenocytes from mice previously immunized to MHV. In this study, we show that, following adoptive transfer, virus-specific CD4 and CD8 T cells rapidly infiltrate the CNS of MHV-JHM-infected RAG1-/- mice. Adoptive transfer of CD4 T cell-enriched donors resulted in more severe clinical disease accompanied by less demyelination than was detected in the recipients of undepleted cells. Macrophage infiltration into the gray matter of CD4 T cell-enriched recipients was greater than that observed in mice receiving undepleted splenocytes. In contrast, CD8 T cell-enriched recipients developed delayed disease with extensive demyelination of the spinal cord. MHV-JHM-infected RAG1-/- mice receiving donors depleted of both CD4 and CD8 T cells did not develop demyelination. These results demonstrate that the development of demyelination following MHV infection may be initiated by either CD4 or CD8 T cells. Furthermore, they show that CD4 T cells contribute more prominently than CD8 T cells to the severity of clinical disease, and that this correlates with increased macrophage infiltration into the gray matter.

T-Lymphocyte Subsets - immunology

CD8-Positive T-Lymphocytes - pathology

CD8-Positive T-Lymphocytes - transplantation

Demyelinating Diseases - virology

CD4-Positive T-Lymphocytes - pathology

Viral Load

CD4-Positive T-Lymphocytes - immunology

Cell Movement - immunology

Murine hepatitis virus - immunology

Spinal Cord - pathology

Demyelinating Diseases - immunology

Epitopes, T-Lymphocyte - immunology

Demyelinating Diseases - pathology

Disease Models, Animal

Mice, Inbred C57BL

T-Lymphocyte Subsets - transplantation

Coronavirus Infections - immunology

Mice, Knockout

Spinal Cord - immunology

Animals

T-Lymphocyte Subsets - pathology

Adoptive Transfer - methods

CD4-Positive T-Lymphocytes - transplantation

Coronavirus Infections - virology

Coronavirus Infections - pathology

Mice

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination
Creators: Gregory F Wu - Program in Neuroscience, Departments of Pediatrics and Microbiology, and University of Iowa College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Ajai A Dandekar
Lecia Pewe
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of immunology (Baltimore, Md. : 1950), Vol.165(4), pp.2278-2286
DOI: 10.4049/jimmunol.165.4.2278
PMID: 10925317
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: NS36592 / NINDS NIH HHS MH2066-03 / NIMH NIH HHS
Language: English
Date published: 08/15/2000
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777349002771

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