IL-13 INDUCES CD34(-CSF MOBILIZED BLOOD TO DIFFERENTIATE IN-VITRO INTO POTENT ANTIGEN-PRESENTING CELLS() CELLS ISOLATED FROM G)

Dendritic cells (DCs), which art antigen presenting cells of potential use in human antitumor vaccination trials, are presently the subject of intense investigation. Many recent studies have reported the possib ility of generating ex vivo large numbers of DCs with high antigen pre senting capacity by the culture of bone marrow or blood progenitors. I n this study, we examined the differentiation into DCs of CD34(+) prog enitors isolated from the G-CSF mobilized blood of 3 healthy donors an d 5 patients with breast cancer and cultured in the presence of GM-CSF + IL-13. The characteristics of the cells were compared to those of c ells obtained in the presence of GM-CSF + TNF alpha. By day 15, one th ird of the bulk cells cultured with IL-13 were CD1a(+)/CD14(-) and str ongly expressed CD1c, CD40, CD80 and HLA-DR. In contrast, cells obtain ed with TNF alpha expressed CD1a on one in three cells but with a cons iderably lower fluorescence intensity than on IL-13-cultured cells and strongly expressed CD14 on more than 50% of cells. CD1a(+)/CD14(-) ce lls emerged in IL-13 cultures at day 5, while in TNF alpha cultures CD 14(+) cells appeared before CD1a(+) cells. Cells grown in the presence of IL-13 had an increased capacity to present antigens to autologous lymphocytes and to stimulate allogeneic T-lymphocytes. This effect was greater than that of cells grown in the presence of TNF alpha. These cells should therefore have greater effector potential in any therapeu tic applications in humans. (C) 1997 Elsevier Science B.V.