Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts

Background. Apoptosis is a cellular phenomenon generally found within rejecting transplants. It may play a role in physiological or therapy-associated deletion of infiltrating lymphocytes or in graft cell destruction. Our study focuses on apoptosis of infiltrating lymphocytes during acute kidney rejection after the initial steroid pulse therapy and on possible prognostic implications. Methods. Renal biopsy specimens of 23 transplant recipients with acute tubulo-interstitial rejection were examined for appearance of apoptosis and compared with 11 transplant biopsies with unspecific organ injury accompanied by lymphocyte infiltration. In all patients, biopsies were performed after steroid pulse therapy, and, after confirmation of rejection, antilymphocytic antibody treatment was carried out. Apoptosis was determined via terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling analysis and confirmed by electron microscopy. Results. Apoptosis of lymphocytes or of tubular epithelium was detected in 11 cases of acute rejection (48%), respectively. Four biopsies showed lymphocytic as well as tubular apoptosis, whereas five sections showed no signs of programmed cell death. In biopsies revealing unspecific injury, tubular cell apoptosis was more frequently found (73%) compared with lymphocyte apoptosis (27%, P<0.05). Most interestingly, patients with a beneficial recovery from acute rejection had a higher proportion of lymphocyte apoptosis compared with patients with poor rejection outcome. The Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without counter-regulating apoptosis. Conclusions. Lymphocyte apoptosis is found as frequently as tubular cell apoptosis in rejecting renal grafts after steroid pulse therapy and might have prognostic value for rejection outcome.