title: Anti-GBM glomerulonephritis: a T cell-mediated autoimmune disease?
abstract: Anti-glomerular basement membrane (GBM) glomerulonephritis, which was among the earliest recognized human autoimmune diseases, is characterized by the presence of anti-GBM antibody. It has been a prototypical example of autoantibody-mediated autoimmune disease. However, decades of research on this disease, based either on clinical observations or experimental models, have revealed that T cell-mediated cellular immunity may potentially be a more important mediator of glomerulonephritis. We have made several breakthroughs in understanding the T cell-mediated mechanism causing this disease in a rat model based on Goodpasture's antigen, non-collagen domain 1 of alpha3 chain of type IV collagen (Col4alpha3NC1). We demonstrated that anti-GBM glomerulonephritis was induced by either passive transfer of Col4 alpha3NC1-specific T cells or active immunization with the nephritogenic T cell epitope of Col4alpha3NC1. Immunization with the T cell epitope also triggered production of anti-GBM antibodies to diversified GBM antigens. Thus, a single nephritogenic T cell epitope alone is sufficient to induce the clinical spectrum of anti-GBM glomerulonephritis, including proteinuria, glomerular injury, and anti-GBM antibody. A possible T cell-mediated mechanism for causing human anti-GBM disease is proposed.
authors.affiliation: University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Yahuan.Lou@uth.tmc.EDU
authors.forename: Ya-Huan
authors.initials: YH
authors.lastname: Lou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D024141:Collagen Type IV / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain