The role of regulatory cells in miniature swine rendered tolerant to cardiac allografts by donor kidney cotransplantation

Joshua D. Mezrich, Jared A. Kesselheim, Douglas R. Johnston, Kazuhiko Yamada, David H. Sachs, Joren C. Madsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1107-1115
Number of pages9
JournalAmerican Journal of Transplantation
Issue number9
StatePublished - Sep 2003


  • CD25
  • Heart transplantation
  • Regulatory cells
  • Swine
  • Tolerance

ASJC Scopus subject areas

  • Transplantation
  • Pharmacology (medical)
  • Immunology and Allergy


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