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.
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.
Haverty
T P
TP
Renal-Electrolyte Section, University of Pennsylvania School of Medicine, Philadelphia 19104.
Watanabe
M
M
Neilson
E G
EG
Kelly
C J
CJ
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
D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D000939:Epitopes; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma