Background: CTLA-4/CD28-B7 and CD40-CD40L interactions constitute two key costimulatory pathways in lymphocyte signalling during experimental allograft rejection. Studies on the expression of these molecules in human transplant rejection are still lacking.
Methods: The immunohistochemical study was performed on renal biopsies obtained for various clinical complications from 25 renal transplant patients. Expression of B7-1 and B7-2 and their counter-receptor CTLA-4, and of CD40 and its counter-receptor CD40L was examined.
Results: In acute rejection a focal intense infiltration of B7-1+ and B7-2+ cells (mainly CD20- CD14+) and of CTLA-4+ T lymphocytes (mainly CD8+) was present. In contrast, CD40 and CD40L were rarely expressed. Accumulations of T lymphocytes were found in the interstitium in the same area containing B7-1+ and B7-2+ cells. The scattered CD40L+ cells found in the T-cell infiltrate exhibited the CD4+ phenotype. In chronic rejection only a few B7-1+, B7-2+ or CTLA-4+ cells were detectable. In contrast, several CD40L+CD4+ cells were present both in the interstitium and in glomeruli. Moreover, an intense expression of CD40 on the endothelium was observed. In patients with cyclosporin nephrotoxicity cells positive for B7-1, B7 2, CTLA-4, CD40, or CD40L were absent.
Conclusions: These results demonstrate a differential expression of costimulatory molecules in renal biopsies of allograft recipients undergoing acute or chronic rejection. Moreover, their detection may prove useful to discriminate rejection from cyclosporin nephrotoxicity.