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Granulocyte Colony-Stimulating Factor Reduces the Capacity of Blood Mononuclear Cells to Induce Graft-Versus-Host Disease: Impact on Blood Progenitor Cell Transplantation
Defu Zeng,
Sussan Dejbakhsh-Jones, and
Samuel Strober
From the Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
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 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.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 453-463
© 1997 by The American Society of Hematology.
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