Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate xenogeneic barrier

Blood. 2002 May 15;99(10):3823-9. doi: 10.1182/blood.v99.10.3823.

Abstract

Induction of tolerance is likely to be essential for successful xenotransplantation because immune responses across xenogeneic barriers are vigorous. Although mixed hematopoietic chimerism leads to stable donor-specific tolerance in allogeneic and closely related xenogeneic (eg, rat-to-mouse) combinations, the ability of this approach to induce tolerance across a highly disparate xenogeneic barrier has not yet been demonstrated. In this study, we investigated the immune responses of murine T cells that developed in mice with pre-established porcine hematopoietic chimerism. Our results show for the first time that induction of porcine hematopoietic chimerism can eliminate the development of antiporcine donor responses in a highly disparate xenogeneic species. Porcine hematopoietic chimeras showed donor-specific nonresponsiveness in the mixed lymphocyte reaction, lack of antidonor IgG antibody production, and acceptance of donor skin grafts. Thus, mixed chimerism is capable of inducing tolerance in a highly disparate xenogeneic combination and may have clinical potential to prevent xenograft rejection. (Blood. 2002;99:3823-3829)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Graft Survival / immunology
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Immunoglobulin G / biosynthesis
  • Kinetics
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Skin Transplantation / immunology
  • Swine
  • T-Lymphocytes / immunology*
  • Transplantation Chimera
  • Transplantation Tolerance*
  • Transplantation, Heterologous / immunology*

Substances

  • Immunoglobulin G