Nephrology Dialysis Transplantation, Vol 13, Issue 3 716-722, Copyright © 1998 by Oxford University Press
L Biancone, G Segoloni, E Turello, D Donati, B Bussolati, G Piccoli and G Camussi
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. Key words: transplantation, rejection,
costimulatory molecules
ORIGINAL ARTICLES
Expression of inducible lymphocyte costimulatory molecules in human renal allograft
Cattedra di Nefrologia, Dipartimento di Scienze Cliniche e Biologiche, Universita di Pavia, Varese, Italy; Laboratorio di Immunopatologia, Catteedra di Nefrologia, Dipartimento di Discipline Medico-Chirurgiche, Corso Dogliotti 14, I-10126 Torino, Italy; Corresponding author
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