Murine interstitial nephritis. I. Analysis of disease susceptibility and its relationship of pleiomorphic gene products defining both immune-response genes and a restrictive requirement for cytotoxic T cells at H-2K.

Abstract

Anti-tubular basement membrance (alpha TBM) disease-producing interstitial nephritis in mice is not dependent on the generation of alpha TBM antibodies. Susceptibility seems to be defined by very private specificities in H-2K. These specificities are pleiomorphic, providing both immune-response genes and identity restrictions for cytotoxic effector functions expressed by a Thy-1.2+, Lyt-2,3+ T cell. These studies establish a role for T cells in the pathogenesis in interstitial nephritis as well as providing further evidence for the role of H-2K in the expression of an autoimmune disease.

Molecular analysis of the helper T cell response in murine interstitial nephritis. T cells recognizing an immunodominant epitope use multiple T cell receptor V beta genes with similarities across CDR3.

“…SJL mice (H-2') 4-6 wk of age (Jackson Laboratory, Bar Harbor, ME) were immunized with RTA/CFA in multiple sites to get aTBM disease (21). Isolation and maintenance of T cell lines and clones.…”

“…In one such model, anti-tubular basement membrane (aTBM) disease in the SJL mouse, autoimmune interstitial nephritis is induced by immunizing susceptible animals with a rabbit renal tubular antigen preparation in complete Freund's adjuvant (RTA/CFA) (21). Animals develop nonpathogenic anti-tubular basement membrane antibodies in 7-10 d (22), with a subsequent renal mononuclear cell infiltrate at 6-8 wk (21,22), that progresses to interstitial fibrosis, end stage renal disease, and death (21,23). The development of aTBM disease depends upon the emergence of a CD4+ helper T cell reactive to the target antigen 3M-1 (7), which is expressed on the surface of proximal renal tubular epithelial cells (24).…”

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

“…Rabbit renal tubular basement membranes were isolated by a differential sieving technique, sonicated, lyophilized, and stored at -20°C (27). Soluble renal tubular antigen (SRTA) was made from these lyophilized membranes by collagenase digestion (28).…”

Rabeprazole-induced acute interstitial nephritis: A case report

“…Whenever AIN is suspected during rabeprazole use, the offending drug should be withheld to avoid permanent renal damage. [2,3] …”