Patients suffering from acute graft-versus-host disease after bone-marrow transplantation have functional CD4+ CD25hi Foxp3+ regulatory T cells

Abstract Acute Graft-Versus-Host Disease (aGVHD), mediated by CD4+ and CD8+ effector T cells, is a life-threatening complication in hematopoietic stem cell (HSC) transplantation. Naturally-occurring CD4+ CD25hi (Foxp3+ ) regulatory T cells (Treg ) have been shown to modulate tolerance to aGVHD in murine graft models. In this report, we investigated their role in the prevention of aGVHD in patients transplanted with bone-marrow-derived HSC. When CD4+ CD25hi Foxp3+ T cells were isolated from bone-marrow grafts, they showed no suppressive activity. The analysis of their function in patients suffering from aGVHD after transplantation revealed a gain of suppressive activity indicating their inability to control the aGVHD induction. Thus, our findings clearly demonstrate that CD4+ CD25+ and CD4+ CD25hi Foxp3+ T cells, when administered in steady-state physiological conditions, do not influence the outcome of aGVHD after bone-marrow transplantation.