Spontaneous interstitial nephritis in kdkd mice. I. An experimental model of autoimmune renal disease.
Mice of the kdkd strain predictably develop a spontaneous tubulointerstitial nephritis after 8 wk of life. In this report we have examined several aspects of the nephritogenic immune response that seemed potentially relevant to the expression of this progressively destructive renal lesion. Of particular interest is that by direct immunofluorescence we were unable to demonstrate the presence of antibodies to determinants in the tubulointerstitium. Serum and kidney eluates from nephritic mice, furthermore, did not stain any renal structures in normal kidney. We did observe, however, that disease could be transferred through kdkd----CBA/Ca bone marrow chimeras, and prevented, in the reverse direction, by CBA/Ca----kdkd chimeras. The development of the interstitial lesion was markedly inhibited by thymectomy with T cell depletion, but disease could not be adoptively transferred with cells or serum from nephritic mice. The interstitial lesions also did not appear in (kdkd X CBA/Ca)F1 hybrids, and the development of disease in kdkd mice could be inhibited by treatment with adoptively transferred T cells from CBA/Ca mice. With these new findings we now hypothesize that susceptibility to the expression of interstitial nephritis in kdkd mice involves the cellular limb of the immune system, and may be related, in part, to alterations in regulatory T cell function.
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000473:pathology; D007116:Immunization, Passive; D007672:Kidney Cortex / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000276:immunology*; D009395:Nephritis, Interstitial / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology