Augumentation of Natural Killer Activity with Exogenous Interleukins in Patients with HIV and Pulmonary Tuberculosis Coinfection

摘要

A depressed level of natural killer (NK) activity is one of the various immunological abnormalities in HIV infection. Defective NK cell functions can be partially restored in vitro by interleukin (IL)-2 and IL-12. IL-15 shares receptor and several biological properties with IL-2. The effect of IL-15 on NK cells in patients with HIV and tuberculosis coinfection (HIV-TB) is unclear. This study examined the cytotoxic activity and cytokine response of NK cells in HIV-TB after stimulation with IL-15 and IL-12/IL-2. The study includes 16 normal healthy subjects (NHS), 15 patients with pulmonary tuberculosis (TB), 15 HIV-infected subjects (HIV), and 15 HIV-TB patients. The cytotoxic activity of NK cells was assessed by dioctadecyloxacarbocyanine dye-based flow cytometry. Interferon-γ present in the culture supernatants was measured by enzyme-linked immunosorbent assay. Basal NK cytotoxicity was found to be lower in HIV-TB (p < 0.05) and HIV when compared to NHS or TB. Maximal NK cytotoxicity (p < 0.05) was observed with an IL-15 and IL-12 combination in all the groups. At a 50:1 effector/target ratio, the mean fold increase in NK cytotoxicity upon stimulation was 2.11 for HIV and 1.84 for HIV-TB. Interferon-γ levels from the stimulated cultures were elevated (p < 0.05) in the HIV and HIV-TB groups. We found no correlation between NK cytotoxicity and CD4 counts in HIV-TB. There is a positive correlation between NK cytotoxicity and interferon-γ secretion for HIV-TB. The combination of IL-15 and IL-12 may have potential to improve the NK activity of HIV and HIV-TB.