INHIBITION OF RESISTANCE TO HEMATOPOIETIC ALLO-GRAFTS IN GRANULOCYTE-COLONY-STIMULATING FACTOR TRANSGENIC MICE

Transplanted allogeneic marrow cells often fail to engraft in a lethal ly irradiated host. This phenomenon, termed resistance to allogeneic m arrow grafts or allo-resistance, is well documented, although its mech anism is not yet understood. Transplantation of major histocompatibili ty complex disparate allogeneic marrow cells into mice transgenic for granulocyte colony-stimulating factor (G-CSF) showed donor-derived spl een 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 t o show CFU-S and died shortly after marrow transplantation. Thus, resi stance to allogeneic marrow cells appeared to be severely impaired in this transgenic mouse. The observation that neutralizing antibody agai nst G-CSF restored allo-resistance in G-CSF transgenic mice and that C FU-S was inducible upon administration of recombinant G-CSF using a mi ni-osmotic pump in non-transgenic recipients, suggests that an elevate d level of this cytokine is important for the inhibition of allo-resis tance. Thus, G-CSF was found to play a role in allogeneic resistance t o marrow grafts and the G-CSF-transgenic mice provide a useful model t o study the inhibition of the resistance. The inhibition of allo-resis tance may be useful in preparing allogeneic bone marrow chimeras in bo th experimental and clinical settings.