Expression of inducible lymphocyte costimulatory molecules in human renal allograft

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.

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.

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.

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.