H-2 Dd transgene suppresses Theiler's virus-induced demyelination in susceptible strains of mice.
Theiler's murine encephalomyelitis virus is a picornavirus which induces chronic immune-mediated central nervous system demyelination and virus persistence in susceptible strains of mice. Using murine strains with congeneic recombinant haplotypes, the H-2D region within the class I major histocompatibility complex has been shown to be important in determining susceptibility/resistance to chronic Theiler's murine encephalomyelitis virus infection. We examined the role of H-2D in demyelinating disease with the use of transgenic D8 mice (H-2Dd, resistant haplotype) crossed to susceptible B10.Q (H-2q) and B10.S (H-2s) mice. Expression of the H-2Dd transgene dramatically suppressed demyelination and reduced the number of virus-antigen positive cells in the spinal cord 45 days following infection. More complete protection was observed in transgenic B10.Q (D8+) mice than in transgenic B10.S (D8+) mice. These experiments support the hypothesis that the immunologic basis of resistance by H-2D is determined by effective antigen presentation which prevents virus persistence and subsequent demyelination.
Rodriguez
M
M
Department of Neurology, Mayo Medical School, Rochester, MN 55905, USA.
David
C S
CS
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D005814:Genes, Viral / Q000276:immunology; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000821:virology; D011051:Poliomyelitis / Q000276:immunology / Q000821:virology*; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology / Q000821:virology; D017945:Theilovirus / Q000235:genetics* / Q000276:immunology; D019076:Transgenes / Q000276:immunology*
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I