Separation of major histocompatibility complex (MHC) and non-MHC gene effects in the development of T cell subsets in relation to susceptibility to cyclosporine A-induced autoimmunity.

摘要: Abstract Many experimental models for autoimmune disease share the requirement of immunization with respective autoantigen. Activation potentially autoreactive cells, already present in peripheral immune system, results development disease. Susceptibility and resistance this type depend on both major histocompatibility complex (MHC) non-MHC encoded genes.1−3 MHC-genes are likely to be involved presentation proper antigenic peptide, whereas genes supposed an active process suppression.4 T cells prevented from displaying their potential by other antagonizing cells.5,6 An alternative way induce autoimmunity is achieved total body irradiation (TBI) subsequent syngeneic bone marrow transplantation (BMT) followed a 4-week period daily Cyclosporine-A (CyA) administration.7 After cessation CyA therapy similar graft-versus-host develops which referred as CyA-induced (CyA-AI); chronic phase model has many similarities human scleroderma.8–10 In thought interfere negative selection thymus resulting increased output self-reactive required elimination autoregulatory cell circuit.11 CyA-AI susceptible Lewis (LEW) rats resistant Brown Norway (BN) differ greatly composition subsets.12,13 To dissect role MHC ratios relation susceptibility CyA-AI, congenic strains (LEW-1N BN-1L) were examined subsets ability develop clinical histological CyA-AI.