Differential effects of interleukin-7 and interleukin-15 on NK cell anti-human immunodeficiency virus activity

Julian J. Lum, David J. Schnepple, Zilin Nie, Jaime Sanchez-Dardon, Georgina L. Mbisa, Jennifer Mihowich, Nanci Hawley, Shanil Narayan, John E. Kim, David H. Lynch, Andrew D. Badley

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The ability of interleukin-7 (IL-7) and IL-15 to expand and/or augment effector cell functions may be of therapeutic benefit to human immunodeficiency virus (HIV)-infected patients. The functional effects of these cytokines on innate HIV-specific immunity and their impact on cells harboring HIV are unknown. We demonstrate that both IL-7 and IL-15 augment natural killer (NK) function by using cells (CD3- CD16+ CD56+) from both HIV-positive and -negative donors. Whereas IL-7 enhances NK function through upregulation of Fas ligand, the effect of IL-15 is mediated through upregulation of tumor necrosis factor-related apoptosis-inducing ligand. The difference in these effector mechanisms is reflected by the ability of IL-15-treated but not IL-7-treated NK cells to reduce the burden of replication-competent HIV in autologous peripheral blood mononuclear cells (PBMC) (infectious units per million for control NK cells, 6.79; for IL-7-treated NK cells, 236.17; for IL-15-treated cells, 1.01; P = 0.01 versus control). In addition, the treatment of PBMC with IL-15-treated but not IL-7-treated NK cells causes undetectable HIV p24 (five of five cases), HIV RNA (five of five cases), or HIV DNA (three of five cases). These results support the concept of adjuvant immunotherapy of HIV infection with either IL-7 or IL-15 but suggest that the NK-mediated antiviral effect of IL-15 may be superior.

Original languageEnglish (US)
Pages (from-to)6033-6042
Number of pages10
JournalJournal of virology
Volume78
Issue number11
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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