Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts

Background. Apoptosis is a cellular phenomenon generally found within rejec ting transplants. It may play a role in physiological or therapy-associated deletion of infiltrating lymphocytes or in graft cell destruction. Our stu dy focuses on apoptosis of infiltrating lymphocytes during acute kidney rej ection after the initial steroid pulse therapy and on possible prognostic i mplications. Methods. Renal biopsy specimens of 23 transplant recipients with acute tubu lo-interstitial rejection were examined for appearance of apoptosis and com pared 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, antilymphocyti c antibody treatment was carried out. Apoptosis was determined via terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling an alysis 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 lymph ocytic 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 apo ptosis (27%, P<0.05). Most interestingly, patients with a beneficial recove ry from acute rejection had a higher proportion of lymphocyte apoptosis com pared with patients with poor rejection outcome. The Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without counter-regulating apo ptosis. Conclusions. Lymphocyte apoptosis is found as frequently as tubular cell ap optosis in rejecting renal grafts after steroid pulse therapy and might hav e prognostic value for rejection outcome.