title: Kidney-induced cardiac allograft tolerance in miniature swine is dependent on MHC-matching of donor cardiac and renal parenchyma.
abstract: Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full-MHC barrier in miniature swine. However, the renal element(s) responsible for kidney-induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic-derived "passenger" cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co-transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC-mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC-matched to each other but MHC-mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC-mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC-mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC-matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: M L
authors.initials: ML
authors.lastname: Madariaga
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Cardiac Surgery, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: S G
authors.initials: SG
authors.lastname: Michel
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: G M
authors.initials: GM
authors.lastname: La Muraglia
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Sekijima
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: V
authors.initials: V
authors.lastname: Villani
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Plastic Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: D A
authors.initials: DA
authors.lastname: Leonard
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Biology, Emmanuel College, Boston, MA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Powell
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Biology, Emmanuel College, Boston, MA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kurtz
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Massachusetts General Hospital, Boston, MA.
authors.forename: E A
authors.initials: EA
authors.lastname: Farkash
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Massachusetts General Hospital, Boston, MA.
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Thoracic Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J S
authors.initials: JS
authors.lastname: Allan
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Plastic Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: C L
authors.initials: CL
authors.lastname: Cetrulo
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: C A
authors.initials: CA
authors.lastname: Huang
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Department of Cardiac Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D064591:Allografts; D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation; D006648:Histocompatibility / Q000276:immunology / Q000502:physiology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation; D008285:Major Histocompatibility Complex / Q000276:immunology / Q000502:physiology*; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000627:therapeutic use; D009927:Tissue and Organ Procurement; D023001:Transplantation Tolerance / Q000276:immunology / Q000502:physiology*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: basic (laboratory) research / science; heart transplantation / cardiology; kidney transplantation / nephrology; tolerance; tolerance: mechanisms
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