MHC haplotype-dependent regulation of MOG-induced EAE in rats.

R Weissert, E Wallström, MK Storch… - The Journal of …, 1998 - Am Soc Clin Investig
R Weissert, E Wallström, MK Storch, A Stefferl, J Lorentzen, H Lassmann, C Linington
The Journal of clinical investigation, 1998Am Soc Clin Investig
Experimental autoimmune encephalomyelitis (EAE) induced in the rat by active
immunization with myelin-oligodendrocyte-glycoprotein (MOG) is mediated by synergy
between MOG-specific T cells and demyelinating MOG-specific antibody responses. The
resulting disease is chronic and displays demyelinating central nervous system (CNS)
pathology that closely resembles multiple sclerosis. We analyzed major histocompatibility
complex (MHC) haplotype influences on this disease. The MHC haplotype does not exert an …
Experimental autoimmune encephalomyelitis (EAE) induced in the rat by active immunization with myelin-oligodendrocyte-glycoprotein (MOG) is mediated by synergy between MOG-specific T cells and demyelinating MOG-specific antibody responses. The resulting disease is chronic and displays demyelinating central nervous system (CNS) pathology that closely resembles multiple sclerosis. We analyzed major histocompatibility complex (MHC) haplotype influences on this disease. The MHC haplotype does not exert an all-or-none effect on disease susceptibility. Rather, it determines the degree of disease susceptibility, recruitment of MOG-specific immunocompetent cells, clinical course, and CNS pathology in a hierarchical and allele-specific manner. Major haplotype-specific effects on MOG-EAE map to the MHC class II gene region, but this effect is modified by other MHC genes. In addition, non-MHC genes directly influence both disease and T cell functions, such as the secretion of IFN-gamma. Thus, in MOG-EAE, allelic MHC class II effects are graded, strongly modified by other MHC genes, and overcome by effects of non-MHC genes and environment.
The Journal of Clinical Investigation