| (1) Differentiation of alloantigen-specific T cells. We discovered that CD103, used by alloresponsive CD8+ T cells to adhere to E-cadherin on transplant tubularcells, is also a marker of regulatory alloreactive CD8+ T cells. Both number and function of these cells are augmented by the immunosuppressieve drugs rapamycin and CPEC. (2) Pathogenesis and significance of subclinical rejection. We found increased expression of SERPIN-B9 in tubularcells of biopsies from patients with subclinical rejection, and hypothesized that SERPIN-B9 protects renal tubular cells from apoptotic cell death. Now, we are studying the cause of increased SERPIN-B9 expression and its regulation. (3) Development of the antiviral immune response after renal transplantation. We study both CD8+ and CD4+ T-cell responses to cytomegalovirus (CMV) after renal transplantation. We demonstrated that dominant CMV-specific CD4+ clones during latency were poorly represented in the acute phase, suggesting that after initial clearance of the virus, strong selection and/or recruitment of novel clones takes place during persistent infection. (4) Optimization of immunosuppressive drug therapy in renal transplantation. We did not find a relationship between CD20+ cellnumber in allografts during rejection and poorer clinical outcome, thus not warranting anti-CD20-antibody therapy for allograft rejection in patients with high CD20+ cell counts in the biopsy. |
