Human Immunodeficiency Virus (HIV) Type-1 GP120-Specific Cell-Mediated Cytotoxicity (CMC) and Natural Killer (NK) Activity in HIV-Infected (HIV+) Subjects: Enhancement with Interleukin-2(IL-2), IL-12, and IL-15 |
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| Affiliation: | 1. Division of Allergy/Immunology, Department of Pediatrics, University of California, Los Angeles, School of Medicine, Los Angeles, California, 90095;2. Immunex Corporation, Seattle, Washington, 98101;1. Department of Health Policy, Vanderbilt University School of Medicine, Nashville, TN, USA;2. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA;3. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA;4. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA;5. Vanderbilt Institute for Global Health, Vanderbilt University School of Medicine, Nashville, TN, USA;6. Friends in Global Health, Abuja, Nigeria;7. University of Nigeria, Enugu, Nigeria;1. Rwanda Zambia Emory HIV Research Group, Department of Pathology, Emory University School of Medicine, Atlanta, GA;2. Department of Obstetrics/Gynecology, Division of Family Planning, Emory University School of Medicine, Atlanta, GA;3. Laney Graduate School, Emory University, Atlanta, GA;4. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA;5. Zambia Emory HIV Research Project, Emmasdale, Lusaka, Zambia;6. Northrise, Ndola, Zambia;1. Heilbrunn Department of Population and Family Health, Columbia University, New York, NY, USA;2. Department of Biostatistics, Columbia University, New York, NY, USA;3. Department of Epidemiology, Columbia University, New York, NY, USA;4. Department of Sociomedical Sciences, Columbia University, New York, NY, USA;5. Mailman School of Public Health and Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA;6. Rakai Health Sciences Program, Kalisizo, Uganda;7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;8. Department of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;9. Department of Pathology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;10. HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, New York, NY, USA;11. Brown School, Washington University, St Louis, MO, USA;12. Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda;13. Department of Disease Control and Environmental Health, Makerere University School of Public Health, Kampala, Uganda;1. Department of Global Health, University of Washington, Seattle, WA, USA;2. Kenya Research and Training Center, University of Washington, Seattle, WA, USA;3. Reproductive and Maternal Health Service Unit, Ministry of Health, Nairobi, Kenya;4. US Centers for Disease Control and Prevention (CDC), Division of Global HIV & TB (DGHT), Nairobi, Kenya;5. Kenya Medical Research Institute, Nairobi, Kenya;6. Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya;7. Department of Epidemiology, University of Washington, Seattle, WA, USA;8. Department of Medicine, University of Washington, Seattle, WA, USA;9. Department of Pediatrics, University of Washington, Seattle, WA, USA |
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| Abstract: | Cell-mediated cytotoxicity (CMC), as mediated by cytophilic antibody to human immunodeficiency virus (HIV) antigens, may be an important defense in HIV-infected (HIV+) patients in response to the virus. In this study the ability of interleukin (IL)-2, IL-12, and IL-15 to enhance natural killer (NK) and gp120-specific CMC of mononuclear cells (MNCs) from HIV+children and adults was examined. NK activity against K562 cells was deficient in HIV+patients compared to controls and could be enhanced by IL-2, IL-12, or IL-15, with the combinations of IL-2 + IL-12 and IL-12 + IL-15 producing more cytotoxicity than individual cytokines. Gp120-specific CMC was significantly higher in patients than in controls. It could be increased by IL-2, IL-12, and IL-15 and further by combining IL-2 and IL-12. When an exogenous source of antibody in the form of hyperimmune HIV-specific immunoglobulin (HIVIG) was present, the response of control MNCs was much higher than that of patients, although gp120-specific cytotoxicity of patients’ MNCs was significantly enhanced (two- to threefold) by the addition of HIVIG. This increment in cytotoxicity due to HIVIG, however, could not be further augmented by cytokines in controls or patients. Our findings suggest multiple cytokine administration to boost NK cell function, together with passive immunotherapy, might offer a new therapeutic approach to benefit HIV+patients. |
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