SELECTIVE-INHIBITION OF RESISTANCE TO HEMATOPOIETIC ALLOGRAFTS BUT NOT REJECTION TO A NATURAL-KILLER-CELL SENSITIVE TUMOR IN TRANSGENIC MICE FOR GRANULOCYTE-COLONY-STIMULATING FACTOR

Transplanted allogeneic marrow grafts often fail to engraft in a letha lly irradiated host. Resistance to hemopoietic allograft is a complexe d phenomenon involving multiple components. To study the involvement o f a hemopoietic cytokine, which was known to play a role for stem cell function, we established lines of mice that were transgenic for human granulocyte colony-stimulating factor (hG-CSF). Elevated and constitu tive expression was found in sera (1,041 +/- 242 pg/ml) of these trans genic mice regardless of their sexes and ages. Strong neutrophilic gra nulocytosis correlated with the elevated G-CSF activity in transgenic mice but not in littermate controls: establishing a functional express ion of this cytokine. In lethally irradiated mice transgenic for G-CSF , infusion of fully allogeneic marrow cells induced donor-derived sple en colony. Growth of hemopoietic allografts appeared to be similar to those of syngeneic marrow cells, which indicates inhibition of resista nce for allogeneic marrow grafts. Because of a positive correlation, i nvolvement of natural killer (NK) cells in resistance of transplanted allografts has been suggested. Inocula of NK-sensitive lymphoma cells were, however, vigorously rejected in the G-CSF-transgenic mice. This observation indicates that G-CSF may play a role in engraftment of tra nsplanted allogeneic marrow grafts and may represent a component of me chanisms of hemopoietic resistance. Furthermore, this result may be an indication that alloresistance and NK cells use different mechanisms to resist each target.