title: Protective modulation of class II MHC gene expression in tubular epithelium by target antigen-specific antibodies. Cell-surface directed down-regulation of transcription can influence susceptibility to murine tubulointerstitial nephritis.
abstract: We have been studying the factors which permit autoimmune injury to the kidney leading to interstitial nephritis. Nonsusceptible mice develop L3T4+ effector T cells which do not recognize their 3M-1 target Ag, nor produce interstitial lesions in the kidney unless proximal tubular class II MHC Ag expression is increased, for example, by rIFN-gamma. Anti-tubular basement membrane/alpha 3M-1-Ab, normally present in such mice after immunization with 3M-1, produce an opposite result by diminishing class II transcription and expression. This unique antibody-ligand interaction on the surface of proximal tubular epithelium secreting 3M-1 serves as a novel protective regulatory response in interstitial parenchyma. The in vitro studies conveyed in this current report suggest that alpha 3M-1-Ab mediate this protective effect by reducing the transcription of mRNA encoding class II gene products. These findings, within the overall complexity of a nephritogenic immune response, demonstrate the important role certain elements may play in maintaining functional nonsusceptibility to autoimmune injury.
authors: Renal-Electrolyte Section, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors: T P
authors: TP
authors: Haverty
authors: M
authors: M
authors: Watanabe
authors: E G
authors: EG
authors: Neilson
authors: C J
authors: CJ
authors: Kelly
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies / Q000302:isolation & purification / Q000502:physiology*; D001667:Binding, Competitive; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II / Q000187:drug effects; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009395:Nephritis, Interstitial / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D000939:Epitopes; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma