title: Adoptive Transfer of Renal Allograft Tolerance in a Large Animal Model.
abstract: Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the adoptive transfer of tolerance to a second, naïve donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for adoptive transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for adoptive transfer of tolerance to a naïve kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for adoptive transfer of tolerance to a naïve donor-matched kidney, depend on peripheral cells that, if not transferred with the LTT kidney, require time to develop in the adoptive host.
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: V
authors.initials: V
authors.lastname: Villani
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J R
authors.initials: JR
authors.lastname: Scalea
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: B C
authors.initials: BC
authors.lastname: Gillon
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J S
authors.initials: JS
authors.lastname: Arn
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Sekijima
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: T A
authors.initials: TA
authors.lastname: Cormack
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: S G
authors.initials: SG
authors.lastname: Moran
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Torabi
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Transplantation Biology Research Center (TBRC) Laboratories, Center for Transplantation Sciences (CTS), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival; D016030:Kidney Transplantation; D013552:Swine; D013556:Swine, Miniature; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
keywords: Kidney (allograft) function/dysfunction; tolerance: experimental