Seebach Jörg
Group Leader
PD Dr. med. Jörg D. Seebach
Name of the Institution
Laboratory for Transplantation Immunology
Department of Internal Medicine, C HOER 31
University Hospital Zurich
Street
Rämistrasse 100
City
8091 Zurich
Phone
+41-44-255 41 34
Group Members
Bettina Baumann, PhD student, baube@usz.ch
Pietro Forte, PhD, pietro.forte@usz.ch
Katja Huggel, Technician, katja.huggel@usz.ch
Florian Martens, MD student, florian.martens@usz.ch
Christine Maurus, MD, christine.maurus@usz.ch
Eva Ruegg, MD student, eva.rueegg@usz.ch
Mårten Schneider, PhD, marten.schneider@usz.ch
Georg Stüssi, MD, georg.stuessi@usz.ch
Regula Müller, Biology student, regulaj.mueller@usz.ch
Main Field(s) of Research, Abstract
Xenotransplantation: Acute vascular rejection in pig-to-primate xenotransplantation includes recognition, infiltration, and damage of grafts by leukocytes. We are studying the molecular interactions between human leukocytes and porcine endothelial cells (EC), the primary location of immune responses against vascularized grafts, to develop tools to inhibit such interactions. We aim at characterize the molecular interactions involved in chemotaxis, adhesion, and transmigration of human leukocytes on porcine EC, the effects of HLA molecules expressed in porcine EC on the immune responses mediated by human NK cells and T cells, the role of Gala1-3Gal expressed on porcine EC on human NK cell responses, and the role of MHC-bound peptides in the recognition of porcine EC by human NK cells and T cells. ABO Incompatibility in Transplantation: We are examining the resistance to natural antibodies against A/B isoagglutinins and the Gala1,3Gal epitope, the former observed in recipients of minor ABO-incompatible bone marrow transplants (BMT). The immediate goal is to analyze the immunological mechanisms leading to spontaneous disappearance of anti-A/B isoagglutinins. Furthermore, the expression of ABH antigens and the association with the clinical outcome of minor ABO-incompatible BMT will be examined The long-term goal is to expand the transplant donor pool by developing therapeutic approaches to prevent hyperacute rejection in allogeneic and xenogeneic transplantation. NK Cells in Allotransplantation: NK cells represent a potential effector population in allotransplantation because of allogeneic MHC incompatibility. In an ex vivo system allogeneic interactions between human NK cells and EC are investigated in a clinical heart transplantation setting. NK cells isolated from recipients at different timepoints post-transplantation are monitored for expression of inhibitory and activating receptors, and tested for adhesiveness and cytotoxicity against pre-isolated EC from donor organs. The aim is to extend the knowledge on NK-cell reactivity in organ transplantation and to identify donor-recipient constellations which may encounter NK-mediated rejection.
Main Fields of Research, Keywords
human, porcine, transplantation, xenotransplantation, xenogeneic, allogeneic, NK cell, T cell, endothelial cell, bone marrow, Gala1,3Gal, chemotaxis, adhesion, transmigration, cytotoxicity, HLA, MHC, ABO antigens. ¨
Special Techniques and Equipment
The methods established in the laboratory include isolation and immortalization of micro and macrovascular endothelial cells, purification of leukocyte subsets from peripheral blood, culture of human and animal cells, transfection of cell lines, flow cytometry, ELISA, and various assays for measuring cytotoxicity and apoptosis, chemotaxis, cell adhesion, transmigration, and agglutination.
Education and Training
Seminar series: Interdisciplinary Transplantation Club (Mondays, 17.00). Group meetings including progress reports and journal clubs (Thursdays, 12.30) We have opportunities for PhD and medical students.
Selected Publications
Matter-Reissmann UB, Sonntag KC, Gilli UO, LeGuern C, Schneider MK, Seebach JD. Human Fas-ligand expression on porcine endothelial cells does not protect against xenogeneic NK cytotoxicity. Xenotransplantation 2003 (in press)
Matter-Reissmann UB, Forte P, Schneider MK, Filguiera L, Groscurth P, Seebach JD. Xenogeneic NK cytotoxicity against porcine endothelial cells is perforin/granzyme B dependent and not inhibited by Bcl-2 overexpression. Xenotransplantation 2002, 9:325-37.
Stüssi G, Seebach LV, Muntwyler J, Passweg J, Schanz U, Gmür J, Gratwohl A, Seebach JD. Consequences of ABO-Incompatibility in Allogeneic Hematopoietic Stem Cell Transplantation. Bone Marrow Transplant 2002, 30:87-93.
Schneider MK, Strasser M, Gilli UO, Kocher M, Moser R, Seebach JD. Rolling Adhesion of Human NK Cells to Porcine Endothelial Cells Mainly Relies on CD49d-CD106 Interactions. Transplantation, 2002, 73:789-796.
Forte P, Pazmany L, Matter-Reissmann UB, Stüssi G, Schneider MK, Seebach JD. HLA-G Inhibits Rolling Adhesion of Activated Human NK Cells on Porcine Endothelial Cells. J Immunol. 2001, 167:6002-8.
Stüssi G, Seebach LV, Muntwyler J, Schanz U, Gmür J, Seebach JD. GvHD and survival after ABO-incompatible Bone Marrow Transplantation. Br J Haematol. 2001, 113:251-253.
Seebach JD, Schneider MK, Comrack CA, LeGuern A, Kolb SA, Knolle PA, Germana S, DerSimonian H, LeGuern C, Sachs DH. Immortalized Bone-Marrow Derived Pig Endothelial Cells. Xenotransplantation 2001, 8:48-61.
Forte P, Matter-Reissmann UB, Strasser M, Schneider MK, Seebach JD. Porcine aortic endothelial cells transfected with HLA-G are partially protected from xenogeneic human NK cytotoxicity. Hum. Immunol. 2000, 61:1066-73.
Seebach JD, Waneck G. Natural killer cells in xenotransplantation. Xenotransplantation 1997, 4:202-211.
Seebach JD., Comrack C, Germana S, LeGuern C, Sachs DH, DerSimonian H. HLA-Cw3 Expression on Porcine Endothelial Cells Protects against Xenogeneic Cytotoxicity Mediated by a Subset of Human NK cells. J Immunol. 1997, 159:3655-3661.
Funding
Swiss National Science Foundation, Research Credit of the University of Zürich, Julius Müller Foundation
URL
Link to "Forschungsdatenbank" of the University
http://www.research-projects.uzh.ch/med/unit41700/area394/index.htm