INTERLEUKIN-12 (IL-12) AUGMENTS CYTOLYTIC ACTIVITY OF NATURAL-KILLER-CELLS TOWARD MYCOBACTERIUM TUBERCULOSIS-INFECTED HUMAN MONOCYTES

We tested the impact of interleukin-12 (IL-12) and of cytotoxic leukocytes (particularly natural killer (NK) cells) from normal and HIV-1-infected subjects on lysis of human monocytes infected with Mycobacterium tuberculosis. Nylon wool nonadherent cells stimulated with interleukin-2 (IL-2) or with IL-12 developed significant killing activity against infected monocytes, with IL-12 being a superior stimulant on a molar basis. Cells of the CD16(+) phenotype mediated most of the cytotoxicity against infected monocytes and this lytic activity was associated with a significant decrease in mycobacterial numbers. When peripheral blood mononuclear cells (PBMC) from HIV-1-infected subjects were examined, it was also found that IL-12 very significantly increased lytic activity against M. tuberculosis-infected cells. Moreover, purified NK cells from normal volunteers or from HIV-1-infected subjects were shown to have elevated lytic activity against M. tuberculosis-infected monocytes after IL-2 or IL-12 stimulation. These data suggest an important involvement of NK cells and their activating stimuli (particularly IL-12) in host resistance to tuberculosis. (C) 1994 Academic Press, Inc.