Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

Chaorui Tian, Xueli Yuan, Jessamyn Bagley, Bruce R. Blazar, Mohamed H. Sayegh, John Iacomini

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The observation that bone marrow derived hematopoietic cells are potent inducers of tolerance has generated interest in trying to establish transplantation tolerance by inducing a state of hematopoietic chimerism through allogeneic bone marrow transplantation. However, this approach is associated with serious complications that limit its utility for tolerance induction. Here we describe the development of a novel approach that allows for tolerance induction without the need for an allogeneic bone marrow transplant by combining non-myeloablative host conditioning with delivery of donor alloantigen by adoptively transferred T cells. CBA/Ca mice were administered 2.5 Gy whole body irradiation (WBI). The following day the mice received Kb disparate T cells from MHC class I transgenic CBK donor mice, as well as rapamycin on days 0-13 and anti-CD40L monoclonal antibody on days 0-5, 8, 11 and 14 relative to T cell transfer. Mice treated using this approach were rendered specifically tolerant to CBK skin allografts through a mechanism involving central and peripheral deletion of alloreactive T cells. These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalClinical Immunology
Volume127
Issue number2
DOIs
StatePublished - May 1 2008

Keywords

  • Negative selection
  • Non-myeloablative conditioning
  • T cells
  • Tolerance
  • Transplantation

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