ACTIVATION OF HUMAN DENDRITIC CELLS BY BACILLUS-CALMETTE-GUERIN

Purpose: Dendritic cells are the most potent antigen presenting cells capable of initiating antitumor immune responses. We previously showed that bacillus Calmette-Guerin (BCG) stimulates cultured human dendrit ic cells. We extended these studies and tested the ability of cultured human dendritic cells to express interleukin IL-8 in response to BCG. We also investigated the T cell stimulatory potential of BCG treated dendritic cells in mixed leukocyte reactions. Materials and Methods: D endritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 6 days in the presence of granulocyte -macrophage colony-stimulating factor and IL-4. Spontaneous and BCG st imulated IL-8 protein release into culture supernatants was measured b y a quantitative immunoassay. IL-8 gene transcription was assessed by reverse transcription-polymerase chain reaction. Untreated and BCG exp osed dendritic cells were compared as stimulators of allogeneic T cell proliferation, measured as [H-3]thymidine incorporation. Results: BCG stimulated IL-8 messenger ribonucleic acid expression and IL-8 protei n release. IL-8 secretion occurred in a dose and time dependent fashio n. BCG induced IL-8 release was further enhanced in the presence of in domethacin. BCG treated dendritic cells were much more potent T cell s timulators than untreated dendritic cells. Conclusions: These data dem onstrate that BCG enhances the production of IL-8, a potent chemokine of T cells and granulocytes, as well as the T cell stimulatory potenti al of human dendritic cells.