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V Antibody response to xenogeneic transfusions: a study in the mouse-to-rat system
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
(English)Manuscript (Other academic)
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90331OAI: oai:DiVA.org:uu-90331DiVA: diva2:162646
Available from: 2003-05-15 Created: 2003-05-15 Last updated: 2015-06-15Bibliographically approved
In thesis
1. Modulation of the Immune Response in Concordant Xenotransplantation
Open this publication in new window or tab >>Modulation of the Immune Response in Concordant Xenotransplantation
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Xenotransplantation, i.e. transplantation between different species, could be a possible solution to the present shortage of organ donors. The immunological response to a xenograft is strong and difficult to suppress. It is driven both by the humoral and cellular part of the immune system. The aim of this thesis was to characterise and modulate this response in a concordant mouse-to-rat model, using both vascularised and non-vascularised grafts.

Exposure of mouse cells or tissue to the circulation of a rat, either through transplantation or transfusions, easily evoked an immune response, consisting of IgM antibodies. A response that was aimed both at antigens present on mouse mononuclear cells and on erythrocytes. A non-immunosuppressed rat rejected a mouse heart graft within three days. The combined use of cyclosporine A (CyA) and deoxyspergualin (DSG) as immunosuppression prevented the rejection of vascularised heart transplants as well as of non-vascularised pancreatic islet grafts. This acceptance was sustained for the heart transplant also after the termination of DSG treatment, but not for the pancreatic islet graft. Furthermore, a second heart graft was accepted when transplanted under monotherapy with CyA 56-154 days after the first transplantation. This finding was interpreted as a humoral unresponsiveness, which could not be reproduced when the primary heart was substituted with a cellular graft, consisting of pancreatic islets or heart cells, or by blood transfusions. However, the rejection of a mouse heart after blood transfusions occurred in the absence of antibodies directed against mouse erythrocytes, in contrast to the observations in non-transfused animals. This indicates that a partial humoral tolerance restricted to the response against erythrocytes can be induced. This mechanism may offer a possibility to induce total humoral tolerance against a xenograft if the appropriate antigens are administered in conjunction with CyA and DSG.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 57 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1258
Keyword
Surgery, Antibodies, blood transfusions, heart, pancreatic islets, tolerance, xenotransplantation, Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-3396 (URN)91-554-5622-7 (ISBN)
Public defence
2003-06-07, Rosénsalen, Ingång 95/96, Akademiska sjukhuset, Uppsala, 12:30
Opponent
Supervisors
Available from: 2003-05-15 Created: 2003-05-15Bibliographically approved

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Lorant, Tomas

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