CHARACTERIZATION OF CELLULAR INFILTRATION AND ADHESION MOLECULE EXPRESSION IN CBA CAH-KDKD MICE WITH TUBULOINTERSTITIAL RENAL-DISEASE/

CBA/CaH-kdkd mice develop a spontaneous and chronic tubulointerstitial renal disease which is characterised by mononuclear cell infiltration , tubular collapse and cystic dilatation of tubules. The pathogenic me chanisms of renal injury have not been fully elucidated in this model. We have analysed the nature of infiltrating cells and the expression of MHC class II antigens, cytokines and adhesion molecules in CBA/CaH- kdkd kidneys at various disease stages. Using immunohistochemical tech niques we found that kdkd kidneys are characterised by abundant macrop hage and dendritic cell infiltration with fewer T cells with CD4+ and CD8+ phenotypes. Interestingly, MHC class II antigens were not induced on renal tubules. The proinflammatory cytokine, TNF-alpha, was marked ly enhanced in kdkd kidney (up to fourfold), whereas the T cell-specif ic cytokine, IFN-gamma, increased less (less than twofold). ICAM-1 and VCAM-1 were markedly overexpressed by injured proximal tubules. ICAM- 2 and PECAM-1 were constitutively expressed on glomerular capillaries and vascular endothelium in normal kidneys and did not change in CBA/C aH-kdkd mice. In conclusion, tubulointerstitial nephritis in CBA/CaH-k dkd mice is characterised by prominent macrophage infiltration and abu ndant expression of ICAM-1 and VCAM-1 on injured renal tubules. The la ck of MHC class II antigens on injured tubules suggests that the kd ge ne defect could generate a secondary renal inflammatory response which is characterised by prominent macrophage infiltration and a relative scarcity of T cells.