Acute rejection of allogeneic hemopoietic progenitors by genetically resistant mice

Natural resistance to hemopoietic allograft results in functional elimination of the graft from the host within 24 to 48 h. The resistance is specific and is directed to the cell surface target structures of an unidentified nature. These determinants are controlled by the major histocompatibility complex-linked hemopoietic histocompatibility (Hh) loci and expressed by cells of the hemopoietic system. In this study, the susceptibility of various hemopoietic progenitors, as well as the nature and the kinetics of the early rejection process, were examined by directly following the functional survival of the grafted progenitors by periodic sampling. In both F1 hybrid and inbred allogeneic hosts, multipotential progenitors for granulocyte-erythrocyte-monocyte-megakaryocyte lineages, bipotential progenitors for granulocyte-monocyte lineages and unipotential progenitors of erythrocyte, granulocyte and monocyte were susceptible to elimination. Therefore, within the limited range of comparisons, neither the lineage, nor the degree of commitment or differentiation determines the susceptibility of hemopoietic progenitors to resistance. Functional elimination of the grafted progenitors from the recipient spleen was irreversible upon cultivation in semisolid medium. The frequency of seeding in the spleen at 3 h was comparable in resistant and susceptible hosts; elimination commenced shortly afterwards and by 24 h after transplantation less than 10% of clonogenic progenitors remained functional. Activation of natural killer cells strengthened pre-existing resistance, but did not convert genetically susceptible mice to resistant. Therefore, the resistance is dependent on an effector mechanism with predetermined specificity.