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


CONCLUSIONS
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.
Zhou
Hui
H
Department of Clinical Laboratory, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. jzhouhui@126.com
Fan
Yan-ying
YY
Wu
Chang-you
CY
D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D009163:Mycobacterium bovis / Q000276:immunology*; D053707:Receptors, Interleukin-12 / Q000378:metabolism*
D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma