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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3829-3835.
Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-01-0393.


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Submitted February 2, 2004
Accepted July 13, 2004

Absence of Clinical GVHD and the In Vivo Induction of Regulatory T cells following Facilitating Cell Transplantation

Yolonda L Colson*, Kenneth Christopher, Jonathan Glickman, Kendra N Taylor, Renee Wright, and David L Perkins

Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA
Laboratory of Molecular Immunology, Renal Division, Brigham and Women's Hospital, Boston, MA, USA
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA

* Corresponding author; email: ycolson{at}partners.org.

Abstract Graft-versus-host disease (GVHD) and failure of engraftment limit clinical bone marrow transplantation (BMT) to patients with a closely matched donor. Engraftment failure of purified allogeneic hematopoietic stem cells (HSC) has been decreased in various BMT models by including donor BM-derived CD8+/{alpha}{beta}{gamma}{delta}TCR- facilitating cells (FC) or CD8+/{alpha}{beta}TCR+ T cells in the BM inoculum. To aggressively investigate GVHD potential of these donor CD8+ populations, a purified cell model of lethal GVHD was established in a murine semiallogeneic parent {Rightarrow} F1 combination. Lethally irradiated recipients were reconstituted with purified donor HSC alone, or in combination with splenic T cells (TSP), BM-derived T cells (TBM), or the FC population. In marked contrast to the lethal GVHD present in recipients of HSC plus TSP or CD8+ TBM, recipients of donor HSC+FC inocula did not exhibit significant clinical or histologic evidence of GVHD. Instead, HSC+FC recipients were characterized by increased splenocyte expression of TGF{beta} and the induction of the regulatory T cell genes, CTLA4, GITR and FoxP3. These findings suggest that the FC, which express a unique FCp33-TCR{beta} heterodimer in place of {alpha}{beta}TCR, permits HSC alloengraftment and prevents GVHD through the novel approach of regulatory T cell induction in vivo.


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