title: Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population.
abstract: BACKGROUND
  To determine the mechanism by which cotransplantation of a donor kidney and heart allograft induces tolerance to both organs in miniature swine, we examined the renal elements responsible for tolerance induction.
  
  
  METHODS
  Recipients received 12 days of cyclosporine, and transplants were performed across a major histocompatibility complex (MHC) class I mismatch. Group 1 animals received heart transplants (n=5); group 2 animals received heart and kidney allografts with no other manipulation (n=4); group 3 animals received heart transplants and donor-specific renal parenchymal cells (n=4); group 4 animals received heart and kidney allografts from lethally irradiated donors (n=7); group 5 animals received irradiated hearts and nonirradiated kidneys (n=2); group 6 animals received nonirradiated hearts and peripheral blood leukocytes from swine MHC matched to recipients and becoming tolerant to donor antigen (n=2); group 7 animals received nonirradiated hearts and donor-specific peripheral blood monocyte cells (PBMC) (n=2).
  
  
  RESULTS
  Animals in group 1 developed vasculopathy and fulminant rejection by day 55. Animals in group 2 never developed vascular lesions. Parenchymal kidney cell infusion (group 3) did not prolong cardiac survival. Animals in group 4 developed arteriopathy by postoperative day (POD) 28. Group 5 recipients accepted allografts without vascular lesions. Adoptive transfer of leukocytes from tolerant swine (group 6) prolonged cardiac graft survival as much as 123 days, whereas donor PBMC infusion (group 7) did not affect cardiac survival or development of arteriopathy.
  
  
  CONCLUSIONS
  Radiosensitive elements in kidney allograft may be responsible for tolerance induction and prevention of chronic vascular lesions in recipients of simultaneous heart and kidney allografts.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Richard S
authors.initials: RS
authors.lastname: Lee
authors.forename: Kwabena
authors.initials: K
authors.lastname: Mawulawde
authors.forename: Louis C
authors.initials: LC
authors.lastname: Benjamin
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Schwarze
authors.forename: Michaella E
authors.initials: ME
authors.lastname: Maloney
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Amoah
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Houser
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D000818:Animals; D006321:Heart / Q000528:radiation effects; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007668:Kidney / Q000166:cytology* / Q000528:radiation effects*; D016030:Kidney Transplantation / Q000276:immunology*; D007937:Leukapheresis; D011836:Radiation Tolerance; D013552:Swine; D013556:Swine, Miniature; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous