Regulatory CD4 super(+)CD25 super(h) super(i) T cells conserve their function and phenotype after granulocyte colony-stimulating factor treatment in human hematopoietic stem cell transplantation

Acute graft-versus-host disease (aGVHD), mediated by CD4 super(+) and CD8 super(+) effector T cells, is a life-threatening complication in hematopoietic stem cell transplantation. CD4 super(+)CD25 super(h) super(i) regulatory T cells (T sub(r) sub(e) sub(g)) have been shown to modulate tolerance to aGVHD in murine models. Based on these observations, we examined their role in the prevention of aGVHD in patients who underwent transplantation with peripheral blood-mobilized hematopoietic stem cells after administration of granulocyte colony-stimulating factor. The effects of the G-CSF on the phenotype, frequency, and function of CD4 super(+)CD25 super(h) super(i) T cells were analyzed in grafts and after transplantation to determine whether these cells were regulatory T cells. CD4 super(+)CD25 super(h) super(i) T cells could be detected at the same frequency before and after granulocyte colony-stimulating factor administration in the donors' peripheral blood. The isolation of these cells from the grafts or from the recipients' peripheral blood after transplantation revealed that they were suppressive to the same extent as T sub(r) sub(e) sub(g) isolated from healthy volunteers. Their number and frequency were estimated in the grafts and the results indicated that protection against aGVHD was not dependent on the T sub(r) sub(e) sub(g) amount transferred to the recipients. Similarly there was no correlation between the number of circulating CD4 super(+)CD25 super(h) super(i) T cells in the recipients' peripheral blood during the early period after transplantation and the outcome of aGVHD.