Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion