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Islet xenotransplantation: An immunological study in the pig-to-mouse model
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Successful clinical xenotransplantation, i.e., transplantation between species, would eliminate the shortage of donor organs. In order to study the acute cellular rejection reaction following discordant xenogeneic transplantation, an experimental pig-to- mouse islet xenotransplantation model was established. Further, immunological processes were evaluated using genetically deficient (knock-out) recipient mice and pharmacological agents exerting cytokine-modulatory actions.

Xenogeneic islet transplantation persists in mice deficient in antibodies, interleukin-6, perforin or granzyme B, suggesting that neither xenoreactive antibodies or interleukin-6 nor granule-mediated lysis are of critical importance to the rejection process. Instead, the immune response following pig-to-mouse islet xenotransplantation bears a close morphological resemblance to a T helper (Th) 1-dependent delayed-type hypersensitivity-reaction with a massive infiltration of macrophages and comparatively small amounts of peripherally accumulated T cells. It may be speculated that islet xenograft destruction is a macrophage-mediated process regulated by T cells. Indeed, Th1-associated cytokines with macrophage-activating properties (interferon-γ and tumor necrosis factor-α) and interleukin-2 seem to be important to islet xenograft rejection, even though other cytokines eventually substitute for the lack of those in a majority of animals.

Key words: xenotransplantation, porcine, islet, in vivo, knock-out mouse,immunohistochemistry, CsA, MDL 201,449A, Ig, FcR, IL-6, perforin, granzyme B,macrophage, eosinophilic granulocyte, T cell, TCR, IFN- g, TNF- a, IL-2.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 43 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 852
Keyword [en]
Oncology, xenotransplantation, porcine, islet, in vivo, knock-out mouse, immunohistochemistry, CsA, MDL 201, 449A, Ig, FcR, IL-6, perforin, granzyme B, macrophage, eosinophilic granulocyte, T cell, TCR, IFN- g, TNF- a, IL-2
Keyword [sv]
Onkologi
National Category
Cancer and Oncology
Research subject
Clinical Immunology
Identifiers
URN: urn:nbn:se:uu:diva-343ISBN: 91-554-4496-2 (print)OAI: oai:DiVA.org:uu-343DiVA: diva2:162773
Public defence
1999-06-02, Rosensalen, Uppsala University Hospital, Entrance 95/96, Uppsala, 13:15
Available from: 1999-05-12 Created: 1999-05-12Bibliographically approved

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