KUPFFER CELL BLOCKADE PREVENTS REJECTION OF HUMAN INSULINOMA CELL XENOGRAFT IN RATS

Alloantigens are recognized by T-cells in the context of both class I and class II antigen, but class II antigens predominate in the recogni tion of xenoantigens. Since class II molecules bind peptides derived f rom exogenous proteins that have been phagocytized and digested into s mall fragments by antigen presenting cells, in the present studies the effect of gadolinium chloride (GdCl3)-induced Kupffer cell blockade o n the survival of discordant insulinoma cell xenografts was investigat ed. Insulinoma cells isolated by means of collagenase from human insul inoma and cultured were transplanted through the v. portae into the li ver of streptozotocin-induced diabetic, male, CFY inbred rats. In the control, streptozotocin-treated rats, the decrease in blood glucose le vel was only transitory, in contrast with the GdCl3-pretreated diabeti c rats, which remained normoglycaemic during the 2-week observation pe riod. Histologically, in the liver and lung of rats pre-treated with G dCl3, large areas of extensively proliferating insulinoma cells were s een, whereas no insulinoma cells were seen in either the liver or the lung of diabetic-control rats, not-treated with GdCl3. These studies s uggest that the Kupffer cells play significant roles in the recognitio n of xenoantigens and the induction of xenograft rejection. (C) 1998 P ublished by Elsevier Science S.A.