Islet xenotransplantation: An immunological study in the pig-to-mouse model
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 852
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
Cancer and Oncology
Research subject Clinical Immunology
IdentifiersURN: urn:nbn:se:uu:diva-343ISBN: 91-554-4496-2OAI: oai:DiVA.org:uu-343DiVA: diva2:162773
1999-06-02, Rosensalen, Uppsala University Hospital, Entrance 95/96, Uppsala, 13:15