Influence of Mycobacterium bovis bacillus Calmette Guerin on in vitro induction of CD1 molecules in human adherent mononuclear cells

Nonpeptide antigens (including glycolipids of microbial origin) can be pres ented to T cells by CD1 molecules expressed on monocyte-derived dendritic c ells. These HLA unrestricted responses appear to play a role in host immuni ty against Mycobacterium tuberculosis and other pathogenic bacteria. It is known that vaccination with Mycobacterium bovis bacillus Calmette-Guerin (B CG) has limited efficacy in many clinical settings, although the reasons fo r its inadequacy remain unclear. Here we have investigated the influence of BCG on the induction of CD1b on human monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is believed to be the principal i nducer of this antigen-presenting molecule. Although BCG alone led to a sli ght induction of CD1b expression, this agent reduced markedly the ability o f GM-CSF to induce high levels of CD1b that were typically observed in unin fected cells. Inhibition of CD1b expression in BCG-infected monocytes was a pparent at both the mRNA transcript and CD1b protein levels. Down-regulatio n of CD1b expression by BCG was mediated, at least in part; by one or more soluble factors and could not be reversed with high concentrations of GM-CS F or a variety of other cytokines. The present results suggest that BCG cou ld diminish the efficiency of CD1-restricted T-cell responses against nonpe ptide mycobacterial antigens by reducing CD1 expression on antigen-presenti ng cells. These findings have potential implications for understanding the nature of the immune response elicited by BCG in humans and suggest potenti al strategies that could be important for the development of better vaccine s for the prevention of tuberculosis.