title: [Mechanism of rejection of islet of Langerhans xenografts].
abstract: For immediately vascularised xenografts, the presence of preformed antibodies associated with the activation of the complement induces a hyperacute humoral rejection in discordant combinations. For neovascularised xenografts, such as the islets of Langerhans, the absence of an initial vascularisation prevents the acute humoral rejection and there is some evidence to suggest that the rejection is cell mediated. To analyse the influence of species response to cellular transplantation, we compared the functional outcome and the immunohistochemical analysis of concordant and discordant xenotransplated islets with allotransplanted islets of Langerhans. In the concordant xenotransplantation experiment, rat (Sprague Dawley) purified islets (N = 600) were transplanted under the kidney capsule of streptozotocin diabetic mice. In the discordant experiment, purified human islets (N = 1000), in the allotransplantation model Balb mouse islets (N = 600) were transplanted under the kidney capsule of C57BL/6 mice. Daily blood glucose levels were monitored until rejection occurred (blood glucose > 11 mMol/L) and kidney biopsies were taken every second day for immunohistological examination. In allotransplanted mice, rejection occurred after a mean of 15 +/- 4 days, in concordant xenotransplanted mice after a mean of 10 +/- 3 days and in the discordant xenotransplanted mice after a mean of 8 +/- 1 days. The immunohistological analysis showed in both xenotransplantation models a deposit of IgM and C3 surrounding the grafted cells, starting at day 1 and persisting until rejection, associated with the presence of Mac-1 positive cells. The intensity of the humoral response was moderate to important in the concordant group, but very strong and unchanged until rejection in the disconcordant group. An invasion with CD4+ and CD8+ cells started between day 4 and 6 in both groups, progressively increasing until rejection. In the allotransplantation model, no humoral response was detectable and the cellular response started between day 10 and 12 after transplantation. We conclude, that a cellular response is involved in the rejection process of both concordant and discordant xenotransplanted islets of Langerhans. Compared to an allotransplantation model, the humoral response does not destroy the function of transplanted islets, but could trigger or accelerate the cell-mediated response.
authors.affiliation: Département de Chirurgie, Hôpital Cantonal Universitaire de Genève.
authors.forename: L
authors.initials: L
authors.lastname: Bühler
authors.forename: S
authors.initials: S
authors.lastname: Deng
authors.forename: E
authors.initials: E
authors.lastname: Andereggen
authors.forename: C
authors.initials: C
authors.lastname: Bubloz
authors.forename: R
authors.initials: R
authors.lastname: Mage
authors.forename: G
authors.initials: G
authors.lastname: Mentha
authors.forename: P
authors.initials: P
authors.lastname: Morel
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D007328:Insulin
vernacular_title: Les mécanismes de rejet dans les xénogreffes d'îlots de Langerhans.