Monocyte-derived dendritic cell precursors facilitate tolerance to heart allografts after total lymphoid irradiation

Background. Previous studies have shown that post-transplant total lymphoid irradiation, anti-thymocyte globulin, and an intravenous donor blood cell infusion induce tolerance to ACI heart allografts in Lewis rat hosts. Methods. In the current study, fresh ACI monocytes and dendritic cell precursors, derived from short-term culture of the latter cells in granulocyte macrophage colony-stimulating factor, were tested for their capacity to prolong heart allograft survival in this model. Results. The experimental results show that significant prolongation of graft survival was achieved after injection of the fresh donor monocytes or a-day or 6-day cultured cells. The a-day cultured cells were most effective, and more than 60% of hosts maintained graft survival for more than 160 days. Ten-day cultured cells and fresh splenic dendritic cells failed to prolong graft survival. Studies of cell surface markers showed that the S-day cultured cells had up-regulated class II major histocompatibility complex and CD80, but not CD86 molecules, On the other hand, the 10-day cultured cells and splenic dendritic cells showed intense expression of all three markers. The latter cells stimulated vigorous proliferative and cell-mediated lympholysis responses in the mixed leukocyte reaction, but the fresh and 2-day cultured cells were weak stimulators. Conclusion. The intravenous injection of donor dendritic cell precursors derived from blood monocytes facilitates long-term acceptance of heart allografts.