title: Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.
abstract: Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sommer
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Gwen
authors.initials: G
authors.lastname: Buechler
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Jansson
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Avsar
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Knöfel
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Jawad
authors.initials: J
authors.lastname: Salman
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hoeffler
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Thierry
authors.initials: T
authors.lastname: Siemeni
authors.affiliation: German Centre for Lung Research, Hannover Medical School, Hannover, Germany.|Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Gottlieb
authors.affiliation: Department of Nuclear Medicine and Radiation Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Johann H
authors.initials: JH
authors.lastname: Karstens
authors.affiliation: German Centre for Lung Research, Hannover Medical School, Hannover, Germany.|Institute for Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Department of Nephrology, Hannover Medical School, Hannover, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Reising
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.affiliation: Richard DeVos Heart & Lung Transplant Program, Frederik Meijer Heart & Vascular Institute, Grand Rapids, MI, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Strüber
authors.affiliation: Department of Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Warnecke
mesh_terms: D064591:Allografts / Q000276:immunology; D000818:Animals; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007962:Leukocytes / Q000378:metabolism; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D016559:Tacrolimus
keywords: donor cell chimerism; heterotopic heart transplantation; lung transplantation; tolerance induction