EARLY EVENTS IN NATURAL RESISTANCE TO BONE MARROW TRANSPLANTATION USE OF RADIOLABELED BONE MARROW CELLS

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Abstract
Natural resistance against the proliferation of splenic colony-forming units (CFU-S) is seen in certain combinations of bone marrow donors and irradiated hosts. In order to examine the early events following bone marrow transplantation and to determine whether genetically determined CFU-S repression is due to elimination of the transplanted cells from the spleen or to inhibition of their proliferation, we labeled proliferating cells in freshly isolated bone marrow or long-term bone marrow cultures (LTBMC) with radioactive I-iododeoxyuridine prior to injection. A heterogeneous mixture of cells was labeled in both freshly isolated marrow and LTBMC; CFU-S precursors were among the cells labeled as indicated by reduction of CFU-S numbers in the radiolabeled cell population. Radiolabeled cells from C57BL/6J, DBA/2J, and B6D2F1 mice were injected into syngeneic, semisyngeneic, and allogeneic irradiated mice that were killed at various times after injection to determine the amount of radioactivity remaining and the organ distribution of the labeled cells; additional mice were killed 7-8 days later to count CFU-S. Retention of label in the spleen was predictive of subsequent CFU-S numbers, suggesting that killing or elimination fo the transplanted cells from the spleen is the cause of CFU-S depression in resistant animals. Further genetic analysis of the survival of the radiolabeled cells in the spleen indicated that mismatching of H-2 homozygous donor cells with the host at H-2D was a prerequisite for resistance and that H-2 heterozygous cells were not resisted in spite of H-2 mismatching. Although natural killer (NK) cell-deficient beige mice were able to resist H-2-nonidentical bone marrow cells, pretreament of the host with anti-asialo GM-1 antibodies completely abrogated natural resistance as assessed by splenic survival or radiolabeled cells. The findings that splenic survival of radiolabeled bone marrow cells reflects the immunogenetic specificity of CFU-S repression and that abrogation of CFU-S repression increases the splenic survival of the labeled cells strengthen the postulate that repression of CFU-S proliferation involves events occurring within the first 24 hr after injection.