The initial phase of graft-versus-host disease is associated with a decrease of CD4+CD25+ regulatory T cells in the peripheral blood of patients after allogeneic stem cell transplantation

The mechanisms that induce and control the alloimmune inflammation of graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (allo-SCT) are still incompletely understood. In the murine system, GvHD can be suppressed by CD4(+)CD25(+) regulatory T cells (TREG), which are generally involved in the suppression of inflammatory reactions. A disruption of the homeostasis between TREG and conventional T cells might therefore be associated with the inflammatory reactions of GvHD. We repetitively measured the frequency of TREG in the peripheral blood of 29 patients within the first 71-373 days after allo-SCT and correlated the results with the clinical course. We demonstrate that the initial phase of GvHD is associated with a significant reduction of TREG in the peripheral blood, while at later stages and during intensified immunosuppressive therapy, increased numbers of TREG appear. These results might indicate a pathogenic role for reduced numbers of TREG in the induction of human GvHD.