GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-STIMULATED HEPATIC DENDRITIC CELL PROGENITORS PROLONG PANCREATIC-ISLET ALLOGRAFT SURVIVAL

Liver-derived dendritic cell (DC) progenitors propagated in liquid cul ture in granulocyte/macrophage colony-stimulating factor exhibit low l evels both of cell surface MDC class II antigens and of counterrecepto rs for CTLA-4/CD28. They fail to stimulate allogeneic T cells in mixed leukocyte cultures. To evaluate their in vivo functional significance , we determined their influence on survival of pancreatic islet allogr afts. Cultured B1O.BR (H2(k); I-E(+)) mouse liver-derived DC progenito rs were injected (2x10(6) i.v.) into streptozotocin-diabetic B10 (H2(b ); I-E(-)) recipients 7 days before transplantation of pancreatic isle ts (700 IEq/mouse) from the same donor strain. No immunosuppressive ag ents were administered. Mean islet allograft survival time was prolong ed from 15.3 days (in animals pretreated with syngeneic cells) to 30.3 days (P<0.001) in mice pretreated with the donor-derived liver cells. In 20% of these animals, islet allograft survival exceeded 60 days. T hese data suggest that liver-derived DC progenitors may contribute bot h to the inherent tolerogenicity of the mouse liver and to its capacit y to protect other allografts of the same donor strain from rejection.