Effect of interleukin (IL)-12 and IL-15 on activated natural killer (ANK) and antibody-dependent cellular cytotoxicity (ADCC) in HIV infection.
The ability of IL-12 and IL-15 to enhance natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNCs) from HIV+ children and their mothers was investigated. MNCs from HIV+ patients were deficient in NK and ADCC activity compared to control MNCs against several target cells. Overnight incubation with IL-15 or IL-12 augmented NK activity of MNCs from both patients and controls, and the combination of IL-12 and IL-15 resulted in the greatest enhancement. ADCC in HIV+ patients against gp120-coated CEM.NKR cells or chicken erythrocytes could also be enhanced by IL-2 or IL-15 in overnight cultures. Culturing MNCs with either IL-2 or IL-15 for 1 week increased the NK activity in patients to levels of controls treated with these cytokines. However, the response to the combination of IL-12 and IL-15 was less than that to IL-15 alone in 1-week cultures. Culturing MNCs with IL-2 and IL-15 for 1 week also increased the percentage of CD16+/CD56+ cells in both patients and controls. Thus, IL-15 can restore the deficient NK activity in patients and may be a candidate for immunomodulative therapy in HIV+ patients.
Lin
S J
SJ
Department of Pediatrics, UCLA Children's Hospital 90095, USA.
Roberts
R L
RL
Ank
B J
BJ
Nguyen
Q H
QH
Thomas
E K
EK
Stiehm
E R
ER
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D019002:CD56 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004338:Drug Combinations; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism
D019002:CD56 Antigen; D004338:Drug Combinations; D015699:HIV Envelope Protein gp120; D019409:Interleukin-15; D017452:Receptors, IgG; D018664:Interleukin-12