FOXP3 expression in peripheral blood rapidly recovers and lacks correlation with the occurrence of graft-versus-host disease after allogeneic stem cell transplantation

CD4(+)CD25(+) regulatory T-cells (Treg cells) that express Foxp3 protein play an important role in inducing and maintaining allogeneic tolerance and can inhibit graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT) in murine models. Thus, it is important to clarify the kinetics of Treg cell recovery and its correlation with the occurrence of GVHD in humans; however, whether there is a correlation between the frequency of Treg cells in peripheral blood and the occurrence of GVHD is controversial. We examined the recovery of Treg cells in peripheral blood after allogeneic SCT by quantitating FOXP3 messenger RNA (mRNA). Full donor chimerism was achieved within I month after SCT in all but 1 case. The ratios of the measured expression levels of FOXP3 mRNA to those of endogenous control genes rapidly recovered to the normal range as early as 1 month after SCT. Cross-sectional as well as longitudinal analyses revealed no significant correlation between the expression level of FOXP3 mRNA and the occurrence of acute and chronic GVHD. This study suggests that the level of FOXP3(+) cells is normal relative to other cell types from the early period after SCT and that their frequency in peripheral blood relative to total leukocytes or T-cells is not indicative of the occurrence of GVHD.