The immunosuppressive agent 15-deoxyspergualin induces tolerance and modulates MHC-antigen expression and interleukin-1 production in the early phase of rat allograft responses.
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Biomedical subjects
Publications and source records attributed to W Müller-Ruchholtz.
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For the study of the epitope distribution on HLA class I molecules, blocking studies were carried out with a competitive radioimmuno assay using 3H labelled monoclonal antibodies (MAbs) against various HLA epitopes. The results were discussed with the help of known HLA amino acid sequences, and the positions of the following epitopes were suggested: A2/Aw69; A2/28; A2/11/25/26/28/29/30/31/Aw33/34; A25/32; Bw4; B7/Bw22,42; Bw6.
The reactivity of a human monoclonal antibody directed against human B and T lymphocytes was tested for the first time at the ultrastructural level. The antigenic sites detected by this antibody were localized on the surface membrane of lymphocytes and, to a lesser extent, in the cytoplasm on membranes of the endoplasmic reticulum and perinuclear envelop of some centroblasts and immunoblasts. Ultrastructural demonstration of target antigen detected by human monoclonal antibodies may be important prior to therapeutic application of these antibodies.
The change in strain-specific urine odors which appears after bone marrow transplantations was systematically examined in mice in order to demonstrate an influence of the hematopoietic system on urinary chemo-signals. Four mice were trained in a Y maze to discriminate two fully allogeneic mouse strains via their urine odors. Urine samples obtained from three inbred strains, from syngeneic reconstituted mice, and from allogeneic reconstituted chimeras were combined in a number of 'transfer of training' tests. The strain-specific urine odors of the recipients were changed by a fully allogeneic bone marrow transplant. Since this change could not be found in syngeneic reconstituted mice, we concluded that it was caused by the graft. Experiments partly failed to demonstrate donor- and recipient-specific components in the urine odor of the chimeras.
Because successful human islet transplantation requires large quantities of viable islets that must be separated from the highly immunogenic exocrine tissue and because handpicking is too time-consuming and laborious to be clinically relevant, a new approach for solving this problem has been established in rat models. It is based on the principle that magnetic microspheres (MMSs) coupled to lectins with binding specificity for the exocrine tissue portion are trapped in an electromagnetic field, thus providing effluent islets of a high degree of purity. In this study our aim was to adapt this principle to human islet preparations. In this context our prime interest was focused on a lectin suitable for human pancreatic tissue. Of 19 different lectins tested, only 1, Wisteria floribunda agglutinin (WFA), is suitable, as shown by immunofluorescence, MMS-lectin binding, and magnetic separation.
An immunogold-silver enhancement technique, which combines effective labeling of viable isolated islets with the ultrastructural resolution of cytological details, was applied in electron microscopy to identify major histocompatibility complex (MHC) structures on islet cells. Incubation of freshly isolated islets from CAP (RT1c) and LEW (RT1l) rats with OX18, an MHC class I antibody, showed strong positive reactivity in macrophages and/or dendritic-like cells (M0-DCs) and vascular endothelial cells (VEs) and a comparatively weaker reactivity in endocrine alpha-, beta-, and delta-cells. With MHC class II antibody OX6 (anti-I-A), M0-DCs were strongly labeled in both rat strains on the surface and on internal structures. Three of five particularly high titered batches of OX6 revealed MHC class II expression on VE and beta-cells. Four days of in vitro culture in combination with a high concentration of glucose and interferon-gamma induced strong enhancement of MHC class I structures and, to a lesser extent, class II structures on beta-cells.
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A new paradigm was constructed using rats as trained animals in order to examine changes appearing in the scent of mice after a fully allogeneic bone marrow transplantation (BMT). Two rats (CAP), deprived of water 20 hours before each training session, were trained in an olfactometer to discriminate two fully allogeneic mice strains (C3H, C57) via their urine odors. Reinforcement for identification of the St was provided by a drop of water. After discrimination was built-up, the reinforcement schedule was reduced stepwise in defined blocks of trials, in order to allow transfer-of-training tests, to which urine samples of allogeneic reconstituted BMT-chimeras (C57----C3H and C3H----C57) were submitted. It was confirmed that the strain-specific urine odors of the recipients were changed by a fully allogeneic BMT. The results also showed that the urine odors of allogeneic reconstituted chimeras differed from the specific urine odor of the donor strain.
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