Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis

The Journal of Clinical Investigation
K M DrescherM Rodriguez

Abstract

The role of various MHC genes in determining the progression of multiple sclerosis (MS) remains controversial. The HLA-DR3 gene has been associated with benign relapsing MS in some genetic epidemiologic studies, but with disease progression in others. We induced demyelination in highly susceptible B10.M and B10.Q mice expressing the DR3 (HLA-DRB1*0301) transgene to determine directly the effects of a human transgene by infecting them with Theiler's murine encephalomyelitis virus (TMEV). DR3+ mice experienced a dramatic reduction in the extent and severity of demyelination compared with DR3- littermate controls, whereas anti-TMEV antibody titers, delayed-type hypersensitivity responses, and levels of infectious virus, virus antigen, and virus RNA were similar in both groups. To address a possible mechanism of how the human transgene is reducing virus-induced demyelination, we analyzed cytokine expression in the lesions and also determined whether B10.M mice can respond to peptides derived from the DR3 molecule. Intense staining for IFN-gamma and IL-4, T helper (TH) 1 and TH2 cytokines, respectively, was found in the lesions of TMEV-infected DR3- mice but not in the DR3+ transgenic mice at day 21 after infection. DR3 peptides eli...Continue Reading

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Citations

Aug 30, 2001·Nature Immunology·V Taneja, C S David
Oct 18, 2000·Rheumatology·E ZanelliR R de Vries
Oct 18, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Lars RåbergAndrew F Read
Aug 6, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Rui YangMing-Hui Zhao
Mar 23, 2007·Annals of the New York Academy of Sciences·Kristen M Drescher, Steven Tracy
Nov 20, 2016·Journal of Neuroinflammation·Bharath WootlaMoses Rodriguez
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K M DrescherM Rodriguez

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