Enhanced antigen-presenting activity and tumour necrosis factor-alpha-independent activation of dendritic cells following treatment with Mycobacterium bovis bacillus Calmette-Guerin

Abstract

Dendritic cells (DCs) are mast potent among the antigen-presenting cells and are believed to be crucial for the initiation of a primary T-cell response to foreign antigens. Mycobacterial infection within macrophages is controlled by cell-mediated immunity. To elucidate the stimulation of immune response by Mycobacterium bovis bacillus Calmette-Guerin (BCG), we purified DCs from precursor cells in human peripheral blood mononuclear cells (PBMC) by culturing them with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and characterized their surface antigen expression. The interaction of cultured DCs with BCC resulted in increased surface expression of several DC-related marker antigens. BCG also induced reduction of endocytosis, enhancement of CD83 expression as well as B7 costimulatory molecules and IL-12 production, suggesting that BCG treatment directly induces DCs to mature. BCG-treated DCs were much more potent antigen-presenting cells in allogeneic immune response than untreated DCs. Moreover, while the neutralization of tumour necrosis factor-alpha (TNF-alpha) significantly blocked the DC maturation induced by lipopolysaccharide (LPS), it could not inhibit the induction of DC maturation by the BCG treatment, indicating that TNF-alpha production plays a minor role in the BCC-