In the setting of hybrid resistance, parental C57BL/6 bone marrow (BM) grafts are vigorously rejected by lethally irradiated (C57BL/6xDBA/2) F1 mice. However, F1 mice pretreated by continuous administration of granulocyte colony-stimulating factor (G-CSF) with a miniosmotic pump before BM grafting developed day-8 splenic colonies of donor origin. This inhibitory effect on rejection was reversible because F1 mice regained the capacity to reject parental BM when the pump ceased functioning. The appearance of only a small number of colonies with the administration of G-CSF soon after BM grafting suggested the importance in producing this inhibitory effect of pre-exposure of host mice to G-CSF. Because G-CSF administration with a syngeneic combination did not influence the number of colonies, an altered distribution of grafted precursors was unlikely. The absence of a reduction in the number of NK1.1-positive cells in G-CSF-treated mice suggested functional impairment of natural killer cells, major effectors in hybrid resistance, but further study is necessary to elucidate the mechanism underlying this phenomenon. However, our results indicate the importance of G-CSF as a regulator in a certain type of immune response and raise the possibility of clinical application in transplantation medicine.
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