Inhibition of resistance to hemopoietic allo-grafts in granulocyte colony-stimulating factor transgenic mice.

Transplanted allogeneic marrow cells often fail to engraft in a lethally irradiated host. This phenomenon, termed resistance to allogeneic marrow grafts or alloresistance, is well documented, although its mechanism is not yet understood. Transplantation of major histocompatibility complex disparate allogeneic marrow cells into mice transgenic for granulocyte colony-stimulating factor (G-CSF) showed donor-derived spleen colonies (CFU-S) and resulted in stable allogeneic chimerism with excellent survival (100% up to 40 days and 89% up to 120 days). Under the same experimental conditions, all the littermate controls failed to show CFU-S and died shortly after marrow transplantation. Thus, resistance to allogeneic marrow cells appeared to be severely impaired in this transgenic mouse. The observation that neutralizing antibody against G-CSF restored allo-resistance in G-CSF transgenic mice and that CFU-S was inducible upon administration of recombinant G-CSF using a mini-osmotic pump in nontransgenic recipients, suggests that an elevated level of this cytokine is important for the inhibition of allo-resistance. Thus, G-CSF was found to play a role in allogeneic resistance to marrow grafts and the G-CSF-transgenic mice provide a useful model to study the inhibition of the resistance. The inhibition of allo-resistance may be useful in preparing allogeneic bone marrow chimeras in both experimental and clinical settings.