Eur J Immunol 2002 Mar;32(3):606-615
Murray P, McGavern D, Pease L, Rodriguez M.
Department of Immunology, Mayo Clinic and Foundation, Rochester, USA.
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.