MONOCYTE-DERIVED DENDRITIC CELL PRECURSORS FACILITATE TOLERANCE TO HEART ALLOGRAFTS AFTER TOTAL LYMPHOID IRRADIATION1

Abstract

BACKGROUND: Previous studies have shown that posttransplant 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 2-day or 6-day cultured cells. The 2-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 2-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.