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

Abstract

Regulatory T cells (T(reg)s) 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 T(reg)s 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 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 T(reg) content may predict for risk of GVHD after SCT. Determining the T(reg) levels in the donor and manipulating T(reg)s early after transplantation may provide a new approach to controlling GVHD.