title: Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.
abstract: Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Avsar
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Jansson
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Sommer
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kruse
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Thissen
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dreckmann
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: A-K
authors.initials: AK
authors.lastname: Knoefel
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Salman
authors.affiliation: Department of Nephrology, Hannover Medical School, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hafer
authors.affiliation: Division of Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hecker
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Buechler
authors.affiliation: Department of Nuclear Medicine and Radiation Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: J H
authors.initials: JH
authors.lastname: Karstens
authors.affiliation: Institute for Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Institute for Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Länger
authors.affiliation: Institute for Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Institute for Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hewicker-Trautwein
authors.affiliation: Department of Applied Cellular Therapy, University of Kiel, Kiel, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ungefroren
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Strüber
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research, Hannover Medical School, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Warnecke
mesh_terms: D000818:Animals; D046528:Chimerism; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D007165:Immunosuppression Therapy; D007519:Isoantigens / Q000276:immunology*; D016040:Lung Transplantation; D008297:Male; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects*; D014019:Tissue Donors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D007519:Isoantigens