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Cellular sources and targets of IFN-gamma-mediated protection against viral demyelination and neurological deficits. Eur J Immunol 2002 03;32(3):606-15

Date

02/22/2002

Pubmed ID

11857334

Pubmed Central ID

PMC5319413

DOI

10.1002/1521-4141(200203)32:3<606::AID-IMMU606>3.0.CO;2-D

Scopus ID

2-s2.0-0036210434   21 Citations

Abstract

IFN-gamma is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-gamma, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler's virus model of multiple sclerosis. During viral infections, IFN-gamma is produced by natural killer (NK) cells, CD4(+) and CD8(+) T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-gamma-mediated protection. To determine the lymphocyte subsets that produce IFN-gamma to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-gamma-production. We demonstrate that IFN-gamma production by both CD4(+) and CD8(+) T cell subsets is critical for resistance to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4(+) T cells make a greater contribution to IFN-gamma-mediated protection. To determine the cellular targets of IFN-gamma-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-gamma receptor. We demonstrate that IFN-gamma receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination.

Author List

Murray PD, McGavern DB, Pease LR, Rodriguez M

Author

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




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

Animals
Antigens, Viral
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cardiovirus Infections
Crosses, Genetic
Demyelinating Diseases
Disease Models, Animal
Disease Susceptibility
Immunotherapy, Adoptive
Interferon-gamma
Lymphocyte Subsets
Mice
Mice, Inbred C57BL
Mice, Knockout
Multiple Sclerosis
Psychomotor Performance
RNA, Viral
Radiation Chimera
Receptors, Interferon
Spinal Cord
Theilovirus