Analysis of the T cell repertoire for myelin basic protein in thymus-grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease inducible in rodents by immunization of brain-specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE-susceptible (LEW) or EAE-resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68-88 sequence of MBP. These findings suggest that the strain-specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.
Department of Immunology, Niigata University School of Medicine, Japan.
Y
Y
Matsumoto
K
K
Kawai
M
M
Fujiwara
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002678:Chimera; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006168:Guinea Pigs; D006649:Histocompatibility Antigens / Q000502:physiology*; D007114:Immunization; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000637:transplantation*
D000939:Epitopes; D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell