GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INDUCES THE DIFFERENTIATION OF MURINE ERYTHROLEUKEMIA-CELLS INTO DENDRITIC CELLS

Dendritic cells (DC) are professional antigen-presenting cells (APC) w ithin the immune system and antigen-pulsed DC can be used as an effect ive vaccine for active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the gen eration of DC. We previously showed that GM-CSF can induce murine eryt hroleukaemia cells (FBL-3) to differentiate into monocyte-like cells. To develop a new vaccinating method to stimulate the host immune respo nse to leukaemia, we further investigate whether FBL-3 cells induced b y GM-CSF can differentiate into DC in the present study. After being t reated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC -145, which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and vascular cell adhesion molecule-1 (VCAM-1) was up-regul ated markedly; the typical morphology of DC were also observed by elec tron microscopy. Functionally, the GM-CSF-induced FBL-3 cells could ap parently stimulate the proliferation of naive allogeneic and autologou s T lymphocytes and induce the generation of specific CTL more efficie ntly than the wild-type FBL-3 cells. Mice immunized with GM-CSF-induce d FBL-3 cells could resist the subsequent challenge with the wild-type FBL-3 cells. Collectively, these data indicate that GM-CSF differenti ates murine erythroleukaemia cells into DC phenotypically, morphologic ally and functionally. FBL-3-derived DC can be used as a new type of v accine. Our results may have important implications for the immunother apy of leukaemia.