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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



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Pubmed Central ID




Scopus ID

2-s2.0-0036210434   21 Citations


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


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

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
Lymphocyte Subsets
Mice, Inbred C57BL
Mice, Knockout
Multiple Sclerosis
Psychomotor Performance
RNA, Viral
Radiation Chimera
Receptors, Interferon
Spinal Cord