Analysis of non-fibroblastic interstitial cells of human pancreas.
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Biomedical subjects
Publications and source records attributed to U Valente.
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A group of 42 sensitized dialysis patients showing high reactivity (81%-100%) against a random panel of peripheral blood lymphocytes (PBL), were analyzed for the presence of autoreactive lymphocytotoxic antibodies. The test was performed at different temperatures (4 degrees C, 22 degrees C, 37 degrees C) with dithiothreitol (DTT) against autologous PBL, EBV-induced autologous B lymphoblasts (A-BCL), K562 cells and T lymphocytes. Thirteen of 42 patients had IgM auto-lymphocytotoxic antibodies. The broadly reactive IgM autoantibodies could be inactivated by treatment with DTT 5 mM and allowed the identification of the presence of autoantibodies alone or in combination with anti-IgG alloantibodies.
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A thrombotic microangiopathy syndrome, clinically and pathologically similar to thrombotic thrombocytopenic purpura (TTP) has been reported in recipients of tissue transplants, including renal and bone marrow allografts. The diagnosis is made only after other causes of microangiopathic hemolytic anemia have been excluded. In this case report we present the outcome of the combination of plasma exchange, dipyridamole and aspirin in the management of a TTP-like syndrome that complicated the post-operative course of liver transplantation.
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The morphology, histological distribution, surface, and enzymatic phenotype of pancreatic HLA-DR+ cells were studied on seven human pancreata, removed from cadaver donors. Frozen and paraffin-embedded pancreas sections were stained with a battery of monoclonal antibodies by indirect immunofluorescence, immunoperoxidase, and immunophosphatase techniques. Two type of cells were found to express HLA-DR surface molecules: endothelial cells and nonfibroblastic non-B and non-T interstitial elements. The latter cells, which were localized both in the exocrine and endocrine portions of the organ, were distinguished in two main families (macrophagic and dendritic) according to their morphology, surface phenotype, and lysosomal enzymatic activities. The phenotype of cells belonging to macrophagic cell family was the following: Leu M1+, Leu M2+, Leu M3+, OKM1+, and OKT6-. In addition these cells were positive for the expression of lysosomal enzymes such as alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (AP). The "dendritic" cell family comprised, among others, cells that were characterized by the presence of numerous finger-like projections, the absence of Leu M1, Leu M2, Leu M3, OKM1, OKT6 surface antigens, and by the negativity for ANAE and AP. These "dendritic looking cells" (DLC) constituted the most represented DR+ cell type within pancreatic islets. The demonstration of dendritic cells within human islets may justify, in humans also, in vitro procedures of intra-islet dendritic cell removal prior to transplantation, in the attempt of islet rejection prevention.
Autoreactive lymphocytotoxic antibodies, which have been found in sensitised dialysis patients, are generally not considered to be harmful to a renal allograft. In this work the presence of such autoreactive antibodies was investigated in the following groups of sensitised endstage renal disease patients: (a) dialysis patients waiting for a first kidney transplant, (b) kidney transplanted patients, and (c) dialysis patients with a previous failed graft. Only sera from the above patients which showed high reactivity (greater than 30%) against peripheral blood lymphocytes of a random cell panel (R-PBL), were screened for the presence of autoreactive lymphocytotoxic antibodies, by testing at different temperatures against autologous T lymphoblasts (PHA-ATL) and EBV-induced autologous B lymphoblasts (EBV-ABL). The results showed that both blood transfusions, and viral infections such as cytomegalovirus (CMV), correlated with the presence of autoreactive antibodies, and that in addition, by using PHA-ATL and/or EBV-ABL as absorbing reagents, it was possible to remove the antibodies. These absorption procedures allowed the identification of the presence of autoreactive antibodies alone or in combination with other alloantibodies.
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The effectiveness of cyclosporine (CsA) as immunosuppressive agent in human kidney graft rejection is well established. However, in spite of efforts to maintain optimal plasma levels, a fraction of transplanted patients undergo rejection episodes and/or irreversible chronic rejection. This suggests that immunosuppression by CsA cannot control the alloreactive response if there is a high degree of histoincompatibility for HLA or non-HLA antigens, or it has little effect on the "high responder" patient. Both possibilities are difficult to test in the human system. A third hypothesis, the existence of individual CsA resistance, was tested by evaluating the in vitro inhibitory activity of CsA on alloreactive T cell lines from several individuals. A different degree of in vitro sensitivity to the drug was observed among alloreactive lines generated from different individuals and among clones obtained from the same bulk line. The variability at the individual level and at the clonal level may account for the onset of CsA-resistant rejection assuming that in vivo a positive selection in the presence of the drug occurs and allows for the resistant clones, if present, to dominate the sensitive ones.
Several procedures for multiple cadaveric organ procurement have been developed for the recent growth of transplantation of extrarenal organs. These techniques permit removal of the kidneys, liver, pancreas and heart from the same donor without jeopardy to the kidneys above all. At the Department of Surgery - Section Transplantation of the University of Genoa in 1983 and 1984 19 multiple organ harvesting have been carried out. The kidneys were transplanted at our Center or at other Nit Center. Two patients received segmental pancreatic allograft. Two livers were sent to other Italian and European Centers and successfully transplanted.