Augumentation of natural killer activity with exogenous interleukins in patients with HIV and pulmonary tuberculosis coinfection.
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-gamma 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-gamma 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-gamma 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.
Ramana Rao
Parasa V
PV
Department of Immunology, Tuberculosis Research Centre (ICMR), Chetput, Chennai 600 031, India.
Rajasekaran
S
S
Raja
Alamelu
A
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy*
D007155:Immunologic Factors; D007378:Interleukins; D007371:Interferon-gamma