IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication

Alexandre Iannello, Mohamed Rachid Boulassel, Suzanne Samarani, Cécile Tremblay, Emil Toma, Jean Pierre Routy, Ali Ahmad

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28 Citations (Scopus)


IL-21 plays an important role in regulating immune response and controlling chronic viral infections. Recently, we reported its decreased serum concentrations and their immunological consequences in HIV-infected persons. In this study, we have investigated how exogenous IL-21 enhances NK cell responses in these persons. We show that the cytokine receptors are expressed equally on all NK cell subsets defined by expression of CD16 and CD56; the cytokine activates STAT-3, MAPK, and Akt to enhance NK cell functions; the STAT-3 activation plays a key role in constitutive and IL-21-mediated enhancement of NK cell functions; the cytokine increases expression of antiapoptotic proteins Bcl-2 and Bcl-XL and enhances viability of NK cells but has no effect on their proliferation; the cytokine enhances HIV-specific ADCC, secretory, and cytotoxic functions, as well as viability of NK cells from HIV-infected persons; it exerts its biological effects on NK cells with minimal stimulation of HIV-1 replication; and the cytokine-activated NK cells inhibit viral replication in cocultured, HIV-infected, autologous CD4+ T cells in a perforin- and LFA-1-dependent manner. These data suggest that IL-21 may serve as a valuable therapeutic tool for enhancing NK cell responses and inhibiting viral replication in HIV-infected patients.

Original languageEnglish
Pages (from-to)857-867
Number of pages11
JournalJournal of Leukocyte Biology
Issue number5
Publication statusPublished - May 2010



  • LFA-1
  • MAPK
  • Perforin
  • STAT-3

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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