TISSUE ANTIGENS IN TUBULOINTERSTITIAL AND VASCULAR REJECTION

We propose that tissue-specific alloantigens are of importance in inte rstitial and vascular rejection. To study this hypothesis we took the following approaches: multivariate analysis on our database (N = 482) was performed, the specificity of T cells cultured from kidneys with r ejection was analyzed, and non-anti-HLA antibodies reactive with endot helium were studied. First we observed that in a cohort study of 482 p atients receiving a cadaveric renal allograft 76 (15.8%) patients deve loped vascular rejection and 115 (23.9%) developed interstitial reject ion. The incidence of vascular rejection was increased in patients wit h delayed graft function, HLA-DR mismatches, a prolonged cold ischemia period, and previous transplantations. Next we examined 40 graft infi ltrating cell (GIG) lines cultured from renal biopsies taken during re jection episodes. Thirteen GIC lines reacted in a donor-specific fashi on to proximal tubular cells (PTEC) but not to donor splenocytes. Thes e GIC recognize polymorphic tissue-specific peptides in the context of allo-MHC Class I. Finally, we studied if nonconventional allo-antigen systems on endothelial cells could be the target of the humoral immun e response during vascular rejection. We found the endothelial monocyt e (EM) system, and another system that is present on endothelial cells and platelets, which can be tested in an antibody-dependent cellular cytotoxicity assay (ADCC).