Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus

Kathryn Trandem; Daniela Anghelina; Jingxian Zhao; Stanley Perlman

doi:10.4049/jimmunol.0903918

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Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus

Journal article

Peer reviewed

Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus

Kathryn Trandem, Daniela Anghelina, Jingxian Zhao and Stanley Perlman

Journal of immunology (Baltimore, Md. : 1950), Vol.184(8), pp.4391-4400

04/15/2010

DOI: 10.4049/jimmunol.0903918

PMCID: PMC2851486

PMID: 20208000

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Abstract

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) develop acute and chronic demyelinating diseases with histopathological similarities to multiple sclerosis. The process of demyelination is largely immune-mediated, as immunodeficient mice (RAG1(-/-) mice) do not develop demyelination upon infection; however, demyelination develops if these mice are reconstituted with either JHMV-immune CD4 or CD8 T cells. Because myelin destruction is a consequence of the inflammatory response associated with virus clearance, we reasoned that decreasing the amount of inflammation would diminish clinical disease and demyelination. Given that regulatory T cells (Tregs) have potent anti-inflammatory effects, we adoptively transferred Tregs into infected C57BL/6 and RAG1(-/-) mice. In both instances, transfer of Tregs decreased weight loss, clinical scores, and demyelination. Transferred Tregs were not detected in the CNS of infected RAG1(-/-) mice, but rather appeared to mediate their effects in the draining cervical lymph nodes. We show that Tregs dampen the inflammatory response mediated by transferred JHMV-immune splenocytes in infected RAG1(-/-) mice by decreasing T cell proliferation, dendritic cell activation, and proinflammatory cytokine/chemokine production, without inducing apoptosis. By extension, decreasing inflammation, whether by Treg transfer or by otherwise enhancing the anti-inflammatory milieu, could contribute to improved clinical outcomes in patients with virus-induced demyelination.

Cell Proliferation

Humans

Coronavirus Infections - physiopathology

Encephalomyelitis, Autoimmune, Experimental - immunology

Adoptive Transfer

T-Lymphocytes, Regulatory - pathology

T-Lymphocytes, Regulatory - immunology

Murine hepatitis virus - immunology

Inflammation Mediators - antagonists & inhibitors

Inflammation Mediators - physiology

Encephalomyelitis, Autoimmune, Experimental - physiopathology

Mice, Inbred C57BL

Immune Tolerance

Murine hepatitis virus - pathogenicity

Coronavirus Infections - immunology

Viral Load - immunology

Mice, Knockout

Encephalomyelitis, Autoimmune, Experimental - therapy

Animals

Coronavirus Infections - therapy

Virulence - immunology

Mice

Mice, Inbred BALB C

T-Lymphocytes, Regulatory - transplantation

HeLa Cells

Chronic Disease

Details

Title: Subtitle: Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus
Creators: Kathryn Trandem - University of Iowa, Iowa City, IA 52242, USA
Daniela Anghelina
Jingxian Zhao
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of immunology (Baltimore, Md. : 1950), Vol.184(8), pp.4391-4400
DOI: 10.4049/jimmunol.0903918
PMID: 20208000
PMCID: PMC2851486
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: T32 AI007511 / NIAID NIH HHS R01 NS036592-12 / NINDS NIH HHS T32 AI007511-14 / NIAID NIH HHS NS36592 / NINDS NIH HHS T32 GM007337 / NIGMS NIH HHS R01 NS036592 / NINDS NIH HHS
Language: English
Date published: 04/15/2010
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777354702771

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