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
Haverty, T.P.; Watanabe, M.; Neilson, E.G.; Kelly, C.J.
Journal of Immunology 143(4): 1133-1141
1989
ISSN/ISBN: 0022-1767 PMID: 2473119 Document Number: 328543
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.