title: Cross-sensitization between xeno- and allo-antigens on subsequent allogeneic and xenogeneic pancreatic islet transplantation in a murine model.
abstract: The number of patients in need of organ transplantation is continuously on the rise. However, because of organ donor shortage, xenotransplantation has been highlighted as an alternative. Among the various porcine organs and tissues, porcine islets are considered to be the best-matching implantable candidates for clinical application based on recent progress in nonhuman primate pre-clinical studies. Nevertheless, before initiation of clinical trials, it should be confirmed whether the requisite xeno-antigen sensitization would have a deleterious effect on subsequent allo-transplantation or vice versa. Therefore, in the present study, the survival rate of islets grafted in naïve recipients was compared with that in cross-sensitized recipients. Enzyme-linked immunosorbent spot, fluorescence-activated cell sorting, and immunohistochemistry were conducted to assess the cellular and humoral immune responses. The survival days of Balb/c mouse islets transplanted into B6 mice that had been previously sensitized with porcine cells (i.e., xeno-sensitized) showed no significant difference from that of naïve B6 mice. Moreover, the survival days of porcine islets transplanted into allo-antigen (Balb/c)-sensitized B6 recipients was not significantly different from that in naïve B6 mice. Furthermore, our data provide the first demonstration that the cellular xenogeneic immune response (against porcine antigen) measured by an enzyme-linked immunosorbent spot assay is not cross-reactive to the allogeneic immune responses in a murine islet transplantation model. These results suggest that clinical application of islet xenotransplantation is not likely to have a deleterious effect on subsequent allogeneic islet transplantation.
authors: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-799, South Korea; Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea. Electronic address: tte9801@hanmail.net.
authors: Hyun-Je
authors: HJ
authors: Kim
authors: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-799, South Korea; Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea. Electronic address: nr.byun@gmail.com.
authors: Nari
authors: N
authors: Byun
authors: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, South Korea. Electronic address: ormssang@gmail.com.
authors: Ohsang
authors: O
authors: Kwon
authors: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-799, South Korea; Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea. Electronic address: chgpark@snu.ac.kr.
authors: Chung-Gyu
authors: CG
authors: Park
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology; D015478:Antigens, Heterophile / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013552:Swine
chemical_list: D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; D007519:Isoantigens
keywords: Cross-reactivity; Islet transplantation; Porcine islet; Sensitization; Xenotransplantation