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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1689-1697. Prepublished online as a Blood First Edition Paper on May 3, 2007; DOI 10.1182/blood-2007-03-079160.
TRANSPLANTATION Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease1 Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD; 2 Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas; 3 Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD; 4 Cell Processing Section, Department of Transfusion Medicine, NIH, Bethesda, MD
Selective depletion (SD) of host-reactive donor T cells from allogeneic stem-cell transplants (SCTs) using an anti-CD25 immunotoxin (IT) is a strategy to prevent acute graft-versus-host disease (aGvHD). There is concern that concurrent removal of regulatory T cells (Tregs) with incomplete removal of alloactivated CD25+ T cells could increase the risk of aGvHD. We therefore measured Tregs in the blood of 16 patients receiving a T-cell–depleted allograft together with anti–CD25-IT–treated SD lymphocytes, in 13 of their HLA-identical donors, and in 10 SD products. Tregs were characterized by intracellular staining for forkhead box protein 3 (FOXP3) and by quantitative reverse-transcription–polymerase chain reaction (qRT-PCR) for FOXP3 gene in CD4+ cells. Patients received a median of 1.0 x 108/kg SD T cells and a stem cell product containing a median of 0.25 x 104/kg residual T cells. Tregs reconstituted promptly after SCT and underwent further expansion. Of the CD4+ T cells in SD products, 1.5% to 4.8% were CD25– Tregs. Acute GvHD (
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
grade II) was restricted to 5 patients whose donors had significantly (P = .019) fewer Tregs compared with those without clinically significant aGvHD. These results suggest that rapid Treg reconstitution can occur following SD allografts, either from CD25– Tregs escaping depletion, or from residual CD25– and CD25+ Tregs contained in the stem-cell product that expand after transplantation and may confer additional protection against GvHD. 
