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

Dendritic cells (DCs) are mast potent among the antigen-presenting cells an d are believed to be crucial for the initiation of a primary T-cell respons e to foreign antigens. Mycobacterial infection within macrophages is contro lled by cell-mediated immunity. To elucidate the stimulation of immune resp onse 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-C SF) and interleukin-4 (IL-4) and characterized their surface antigen expres sion. The interaction of cultured DCs with BCC resulted in increased surfac e expression of several DC-related marker antigens. BCG also induced reduct ion of endocytosis, enhancement of CD83 expression as well as B7 costimulat ory molecules and IL-12 production, suggesting that BCG treatment directly induces DCs to mature. BCG-treated DCs were much more potent antigen-presen ting cells in allogeneic immune response than untreated DCs. Moreover, whil e the neutralization of tumour necrosis factor-alpha (TNF-alpha) significan tly blocked the DC maturation induced by lipopolysaccharide (LPS), it could not inhibit the induction of DC maturation by the BCG treatment, indicatin g that TNF-alpha production plays a minor role in the BCC-induced DC matura tion. However, the neutralization of TNF-alpha resulted in decreased IL-12 production by activated DCs. These results suggest that infection with BCG might evoke direct activation and maturation of DC and the general immune s timulant effect of BCG might be related with the activation of DCs.