BRUCELLA-ABORTUS AS A POTENTIAL VACCINE CANDIDATE - INDUCTION OF INTERLEUKIN-12 SECRETION AND ENHANCED B7.1 AND B7.2 AND INTERCELLULAR-ADHESION MOLECULE-1 SURFACE EXPRESSION IN ELUTRIATED HUMAN MONOCYTES STIMULATED BY HEAT-INACTIVATED B-ABORTUS

Development of a vaccine which is capable of generating a strong cellu lar immune response associated with gamma interferon (IFN-gamma) produ ction and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Bru cella abortus can induce IFN-gamma secretion by T cells, In the presen t study, we demonstrate that B. abortus and lipopolysaccharide (LPS) f rom B. abortus can induce IL-12 p40 mRNA expression and protein secret ion by human elutriated monocytes (99% pure), p40 mRNA was detected wi thin 4 h, and p40 protein could be measured at 24 h. This induction wa s abrogated by anti-CD14 monoclonal antibody, suggesting that monocyte s recognize B. abortus via their receptor for LPS. The biological acti vity of IL-12 secreted by B. abortus-stimulated monocytes was demonstr ated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K 562 target cells, B. abortus was shown to rapidly increase the express ion of the costimulatory molecules B7.1 and B7.2 and intercellular adh esion molecule 1 on human monocytes. Together, these data indicate tha t B. abortus can directly activate human monocytes and provide the cyt okine milieu which would direct the immune response towards Th1-Tc1 di fferentiation.