title: Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model.
abstract: The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Lei
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Shi
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Z
authors.initials: Z
authors.lastname: Machaidze
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: C
authors.initials: C
authors.lastname: Schuetz
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: P N
authors.initials: PN
authors.lastname: Martins
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Oura
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: E A
authors.initials: EA
authors.lastname: Farkash
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: I A
authors.initials: IA
authors.lastname: Rosales
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Stott
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Soohoo
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Boskovic
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: K
authors.initials: K
authors.lastname: Cappetta
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: O M
authors.initials: OM
authors.lastname: Nadazdin
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: H
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: G
authors.initials: G
authors.lastname: Benichou
authors.affiliation: Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D017710:Lymphocyte Transfusion / Q000379:methods*; D010865:Pilot Projects; D011323:Primates; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D007519:Isoantigens
keywords: Donor-specific hyporesponsiveness; donor-specific transfusion/antigen delivery; graft survival; tolerance; tolerance: depletion