title: The role of regulatory cells in miniature swine rendered tolerant to cardiac allografts by donor kidney cotransplantation.
abstract: To determine the mechanism by which cotransplantation of a kidney allograft induces tolerance to a donor heart in miniature swine, we examined the role of CD25+ cells in heart/kidney recipients. Tolerance was induced to class-I MHC mismatched hearts by cotransplanting a donor-specific kidney with a 12-day course of cyclosporine. Peripheral blood leukocytes (PBL) were isolated from tolerant heart/kidney recipients and used in cell-mediated lympholysis (CML) coculture assays as either unmodified PBL, PBL enriched for CD25+ cells or PBL depleted of CD25+ cells to assess their ability to suppress CML responses of naïve recipient-matched leukocytes against mismatched target cells. Primed PBL from tolerant heart/kidney recipients completely suppressed lysis by naïve cells. Complete suppression of the response of naïve recipient-matched leukocytes against donor-matched target cells was lost following the depletion of CD25+ cells from tolerant heart/kidney animal PBL, but it was reestablished by incubation of naïve cells with small populations of CD25+ cells from tolerant heart/kidney animals. These data suggest that peripheral blood from tolerant heart/kidney recipients contains regulatory cells that, upon priming, can suppress the response of naïve-matched PBL in coculture CML assays, and that suppression appears to be dependent on cells expressing CD25.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: Jared A
authors.initials: JA
authors.lastname: Kesselheim
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Johnston
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D008285:Major Histocompatibility Complex; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology; D023001:Transplantation Tolerance