Selective inhibition of resistance to hemopoietic 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 lethally irradiated host. Resistance to hemopoietic allograft is a complexed phenomenon involving multiple components. To study the involvement of 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 constitutive expression was found in sera (1,041 ± 242 pg/ml) of these transgenic mice regardless of their sexes and ages. Strong neutrophilic granulocytosis correlated with the elevated G-CSF activity in transgenic mice but not in littermate controls, establishing a functional expression of this cytokine. In lethally irradiated mice transgenic for G-CSF, infusion of fully allogeneic marrow cells induced donor-derived spleen colony. Growth of hemopoietic allografts appeared to be similar to those of syngeneic marrow cells, which indicates inhibition of resistance for allogeneic marrow grafts. Because of a positive correlation, involvement 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 transplanted allogeneic marrow grafts and may represent a component of mechanisms of hemopoietic resistance. Furthermore, this result may be an indication that alloresistance and NK cells use different mechanisms to resist each target.