IMMUNOBIOLOGY High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT

Regulatory T cells (Tregs) that constitu-tively 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 coex-pression of FOXP3 on CD4 T cells in 32 donor SCTs infused into HLA-matched sib-lings and examined GVHD incidence in re-spective recipients. High CD4FOXP3 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-cell–depleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4FOXP3 T-cell compartment. A low CD4FOXP3 T-cell count early after SCT (day 30) was associated with an increased risk of GVHD, and the ratio of CD4FOXP3 T cells to CD4CD25FOXP3 T cells was signifi-cantly reduced in patients with GVHD, sug-gestingdiminishedcontrolofeffectorTcells. 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 transplanta-tion may provide a new approach to control-ling GVHD. (Blood. 2006;108:1291-1297) © 2006 by The American Society of Hematolog