1. Phylogenetic disparity influences the predominance of direct over indirect pathway of antigen presentation in islet xenotransplantation
- Author
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Thierry Berney, Domenico Bosco, Axel Andres, Jose Oberholzer, Philippe Morel, Christian Toso, Thomas Wekerle, Pascal Alain Robert Bucher, Gang Mai, Leo Buhler, and Z Mathe
- Subjects
Graft Rejection ,Male ,endocrine system ,Cellular immunity ,Time Factors ,Transplantation, Heterologous/immunology ,Xenotransplantation ,medicine.medical_treatment ,Lymphocyte ,Transplantation, Heterologous ,Antigen presentation ,Islets of Langerhans Transplantation ,Biology ,Indirect pathway of movement ,Rats, Sprague-Dawley ,Mice ,In vivo ,medicine ,Animals ,Humans ,Antigen Presentation/immunology ,Phylogeny ,Antigen Presentation ,Graft Survival/immunology ,Transplantation ,geography ,geography.geographical_feature_category ,ddc:617 ,Graft Survival ,Graft Rejection/immunology ,Islet ,In vitro ,Rats ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Immunology ,Surgery ,Islets of Langerhans Transplantation/immunology ,Lymphocyte Culture Test, Mixed - Abstract
Background Cellular immunity plays a major role in rejection of xenografted islets. Depending on the phylogenetical disparity, direct or indirect antigen presentation is predominant. The aim of this study was to analyze in vitro the predominance of direct or indirect presentation, and in vivo the effect of macrophage depletion on concordant and discordant islet xenograft survival. Materials and methods In vitro, we performed mouse antirat and mouse antihuman mixed lymphocyte reactions (MLR) after depletion of responder or stimulator antigen-presenting cells. In vivo, streptozotocin-induced diabetic C57BL/6 mice were treated by gadolinium chloride to deplete macrophages and rat or human islets were transplanted under the kidney capsule. Islet function was followed by glycemia and xenografts were analyzed at regular intervals for histology. Results Mouse antirat MLR showed a predominant direct antigen presentation pathway, whereas in mouse antihuman MLR, direct and indirect pathways were similarly involved. Survival of rat islets was not modified by GdCl therapy. In contrast, survival of human islets was significantly prolonged in GdCl-treated mice. Macrophage infiltration was decreased in concordant and discordant GdCl-treated xenografts at day 4, compared to controls. At day 15, macrophage infiltration was similar in all groups. Discussion Our results indicate that direct antigen presentation is dominant in rejection of concordant islet xenografts and cannot be influenced by host macrophage depletion. Both direct and indirect antigen presentation are involved in rejection of discordant xenogeneic islets. Macrophage depletion or inhibition should be considered as therapeutic tool for discordant islet xenotransplantation.
- Published
- 2005