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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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TRANSPLANTATION
Absence of clinical GVHD and the in vivo induction of regulatory T cells after transplantation of facilitating cells
Yolonda L. Colson,
Kenneth Christopher,
Jonathan Glickman,
Kendra N. Taylor,
Renee Wright, and
David L. Perkins
From the Division of Thoracic Surgery, Department of Surgery, Department of Pathology, and Laboratory of Molecular Immunology, Renal Division, Brigham & Women's Hospital, Boston, MA.
Graft-versus-host disease (GVHD) and failure of engraftment limit clinical bone marrow transplantation (BMT) to patients with closely matched donors. Engraftment failure of purified allogeneic hematopoietic stem cells (HSCs) has been decreased in various BMT models by including donor BM–derived CD8+/    TCR- facilitating cells (FCs) or CD8+/TCR+ T cells in the BM inoculum. To aggressively investigate the GVHD potential of these donor CD8+ populations, a purified cell model of lethal GVHD was established in a murine semiallogeneic parent  F1 combination. Lethally irradiated recipients were reconstituted with purified donor HSCs 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 HSCs 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 transforming growth factor- (TGF-) and the induction of the regulatory T-cell genes CTLA4, GITR, and FoxP3. These findings suggest that the FCs, which express a unique FCp33-TCR heterodimer in place of TCR, permits HSC alloengraftment and prevents GVHD through the novel approach of regulatory T-cell induction in vivo.
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