BACILLUS-CALMETTE-GUERIN MYCOBACTERIA STIMULATE HUMAN BLOOD DENDRITICCELLS

Bacillus Calmette-Guerin (BCG) mycobacteria have been used as adjuvant in the active immunotherapy of various human cancers. In addition, de ndritic cells, which are the most potent antigen-presenting cells, hav e been shown to be capable of initiating anti-tumor immune responses. Here we investigated the effects of BCG on dendritic cells cultured fr om human blood. Addition of BCG resulted in rapid homotypic adhesion o f dendritic cells. Moreover, BCG concentrations ranging from 10(4) to 10(6) bacteria/ml enhanced expression of the dendritic-cell-maturation antigen CD83 and of the T-cell co-stimulator CD86 (B7-2) in a dose-de pendent manner. Concomitant with the increase of CD83 and CD86 express ion, the cells lost the ability to capture soluble antigens, as determ ined by the exclusion of fluoresceinated Dextran molecules. Strikingly , the same dosages of BCG-bacteria stimulated TNF-alpha-gene transcrip tion and TNF-alpha-protein release from dendritic cells in a dose-depe ndent fashion. BCG infection of dendritic cells in the presence of a n eutralizing antibody directed against TNF-alpha inhibited CD83 express ion by more than 50% indicating that the BCG-induced maturation of den dritic cells was at least partially mediated by dendritic-cell-derived TNF-alpha. The finding that BCG activates the most potent antigen-pre senting cells reveals a plausible immunological mechanism of the occas ionally observed anti-tumor activity of BCG. (C) 1997 Wiley-Liss, Inc.