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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1291-1297.
Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-02-003996.
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IMMUNOBIOLOGY
High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT
Katayoun Rezvani,
Stephan Mielke,
Mojgan Ahmadzadeh,
Yasemin Kilical,
Bipin N. Savani,
Josette Zeilah,
Keyvan Keyvanfar,
Aldemar Montero,
Nancy Hensel,
Roger Kurlander, and
A. John Barrett
From the Stem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH); the Department of Surgery, National Cancer Institute, NIH; and the Department of Laboratory Medicine, NIH, Bethesda, MD.
Regulatory T cells (Tregs) that constitutively express FOXP3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in humans. To determine whether regulatory T cells in allogeneic stem cell transplants (SCTs) ameliorate GVHD after transplantation, we quantitated the coexpression of FOXP3 on CD4+ T cells in 32 donor SCTs infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4+FOXP3+ T-cell count in the donor was associated with a reduced risk of GVHD. We monitored Tregs during immune reconstitution in 21 patients with leukemia undergoing a T-celldepleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4+FOXP3+ T-cell compartment. A low CD4+FOXP3+ T-cell count early after SCT (day 30) was associated with an increased risk of GVHD, and the ratio of CD4+FOXP3+ T cells to CD4+CD25+FOXP3 T cells was significantly reduced in patients with GVHD, suggesting diminished control of effector T cells. Our findings suggest that graft Treg content may predict for risk of GVHD after SCT. Determining the Treg levels in the donor and manipulating Tregs early after transplantation may provide a new approach to controlling GVHD.

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