Tolerance to self-antigens in transgenic mice.
Transgenic mice represent a versatile experimental approach for understanding the pathways by which the immune system regulates responsiveness to self-antigens, thereby establishing self-tolerance. The introduction of immunoglobulin and T cell receptor genes with specificity for self-antigens into the germline of mice has enabled the fate of self-reactive lymphocyte precursors to be followed in vivo. The influence of both developmentally regulated, and tissue-specific gene expression on tolerance to self-antigens has been addressed using transgenic mice expressing novel self-antigens under the transcriptional control of heterologous gene promoters. The generation of transgenic mice expressing structurally altered forms of self-antigens has allowed the role of antigen-processing in the induction of tolerance to be examined. Significantly, while these studies have confirmed the classically derived principles of immunological self-tolerance, they also point to the existence of pathways, as yet undefined, by which tolerance to self-antigens may be implemented and maintained.
Adams
T E
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Department of Veterinary Preclinical Sciences, University of Melbourne, Parkville, Victoria, Australia.
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D005813:Genes, Synthetic; D006182:H-Y Antigen / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D007107:Immune System / Q000196:embryology; D007108:Immune Tolerance / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D008954:Models, Biological; D009928:Organ Specificity; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000502:physiology
D001324:Autoantigens; D006182:H-Y Antigen; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins