Granulocyte Colony-stimulating Factor Reduces the Capacity of Blood Mononuclear Cells to Induce Graft-versus-host Disease: Impact on Blood Progenitor Cell Transplantation

The feasibility of transplanting peripheral blood mononuclear cells (PBMC) from granulocyte colony-stimulating factor (G-CSF)-treated normal human donors to myeloablated allogeneic hosts has been demonstrated recently. The current work examined the ability of recombinant G-CSF to alter peripheral blood T-cell function and graft-versus-host disease (GVHD) in a murine model of allogeneic G-CSF-mobilized PBMC transplantation. Administration of recombinant G-CSF to C57BL/Ka mice markedly increased the capacity of PBMC to reconstitute lethally irradiated syngeneic hosts. T- and B-lineage lymphocytes were depleted about 10-fold in the bone marrow of the treated mice, and the T-cell yield in the blood was increased about fourfold. The ability of PBMC or purified CD4+ and CD8+ T cells to induce acute lethal GVHD in irradiated BALB/c mice was reduced after the administration of G-CSF. This was associated with decreased secretion of interferon gamma and interleukin-2 (IL-2) and an increased secretion of IL-4. The donor cell inoculum, which was most successful in the rescue of irradiated allogeneic hosts, was the low-density fraction of PBMC from G-CSF-treated mice. These low-density cells were enriched for CD4-CD8-NK1.1+ T cells and secreted about 10-fold more IL-4 than the unfractionated cells from the G-CSF-treated donors.