[Bacillus Calmette-Guérin enhances the function of human nature killer cells by inducing IL-12 production and IL-12R expression].

AIM

To study the effect and mechanism of BCG on human nature killer cells.

METHODS

PBMC or purified NK cells were isolated from normal human peripheral blood with negative anti-Mycobacterium tuberculosis antibody and cultured with BCG, IL-12, BCG plus IL-12 and BCG plus anti-IL-12R beta 1 mAb (2B10), respectively. The levels of IFN-gamma and IL-12p40 in the culture supernatants were measured by ELISA. The frequency of IFN-gamma and granzyme B producing cells were analyzed by ELISpot. The cytolytic activity was detected by MTT reduction assay. The surface expression of IL-12R beta 1 on NK cells was detected by flow cytometry.

RESULTS

BCG significantly induced IFN-gamma production by PBMC in a dose-dependent manner. When PBMC was stimulated with BCG, the frequency of granzyme B producing cells was higher than that in unstimulated PBMC (P<0.05). BCG enhanced the cytotoxic activity of PBMC. BCG alone didn't induce IFN-gamma production by purified NK cells, but it can augment IL-12-induced IFN-gamma production by purified NK cells. The cytotoxic activities of BCG-stimulated and unstimulated purified NK cells were not significantly different (P>0.05). BCG induced IL-12 production by PBMC in a dose-dependent manner and enhanced IL-12R beta 1 expression on different subsets of NK cells. Blocking the effect of IL-12 by anti-IL-12R beta 1 mAb (2B10) inhibited BCG-induced IFN-gamma production and granzyme B releasing by PBMC.

CONCLUSION

BCG can indirectly promote biologic activity of NK cells and the production of endogenous IL-12 combined with up-regulation IL-12R beta 1 expression on the surface of NK cells is a part of the mechanisms of IL-12 on human NK cells.