GRANULOCYTE-COLONY-STIMULATING FACTOR REDUCES THE CAPACITY OF BLOOD MONONUCLEAR-CELLS TO INDUCE GRAFT-VERSUS-HOST DISEASE - IMPACT ON BLOODPROGENITOR-CELL TRANSPLANTATION

The feasibility of transplanting peripheral blood mononuclear cells (P BMC) from granulocyte colony-stimulating factor (G-CSF)-treated normal human donors to myeloablated allogeneic hosts has been demonstrated r ecently. 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 transplant ation. Administration of recombinant G-CSF to C57BL/Ka mice markedly i ncreased the capacity of PBMC to reconstitute lethally irradiated syng eneic hosts. T- and B-lineage lymphocytes were depleted about 10-ford in the bone marrow of the treated mice, and the T-cell yield in the bl ood 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 associat ed 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-de nsity cells were enriched for CD4(-)CD8(-)NK1.1(+) T cells and secrete d about 10-fold more IL-4 than the unfractionated cells from the G-CSF -treated donors. (C) 1997 by The American Society of Hematology.