Apoptosis and expression of cytotoxic T lymphocyte effector molecules in renal allografts

Cytotoxic T lymphocyte (CTL) mediated apoptosis is thought to play a major role in the rejection of renal allografts following transplantation, howeve r, the CTL effector mechanism that is primarily responsible for immunologic al rejection is unknown. The two major effector pathways of CTL killing whi ch lead to apoptosis involve the Fas/Fas ligand (Fas L) lytic pathway, and the perforin/granzyme degranulation pathway. The expression of Cn effector molecules which influence these pathways include Pas, Pas L and TiA-1 (cyto toxic granule protein). This study has investigated apoptosis by in situ te rminal deoxytransferase-catalysed DNA nick end labelling (TUNEL), and the e xpression of CTL effector molecules by immunohistochemistry, in renal allog raft biopsies obtained from patients following kidney transplantation. Rena l biopsies were classified into three histological groups; acute cellular r ejection, chronic rejection, or no rejection. The extent of T-cell infiltra tion of renal tissues was assessed by immunohistochemical staining with an anti-CD3 monoclonal antibody. Numerous TUNEL positive cells were detected i n all transplant biopsies examined; these consisted mainly of renal tubular cells and infiltrating cells, with some TUNEL positive cells also detected in the glomeruli. In the case of normal kidney tissue, renal cells also st ained positive for TUNEL but there was no lymphocytic infiltration. There w as significantly more T-cell infiltration observed in acute rejection biops ies compared to the no rejection biopsies. In the case of Pas L expression, there was little expression in all three biopsy groups, apart from one cas e of chronic rejection. Conversely, although there were no significant diff erences in TiA-1 expression between the three biopsy groups, TiA-1 expressi on was more prominent in acute rejection biopsies. Furthermore, Pas express ion was significantly decreased in acute rejection biopsies when compared t o those of chronic and no rejection in which Fas was predominantly localize d in the renal tubular cells. These results indicate that the mechanism of CTL killing leading to the rejection of renal allografts may be different i n acute and chronic rejection. Moreover, our data indicate the potential fo r cytotoxic granule-based CTL killing in acute renal allograft rejection bu t not in chronic rejection.