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

Journal of Leukocyte Biology
Alexandre IannelloAli Ahmad

Abstract

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-X(L) 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 e...Continue Reading

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Citations

May 5, 2009·Médecine sciences : M/S·Alexandre Iannello, Ali Ahmad
Jul 1, 2011·Journal of Biomedicine & Biotechnology·Raffaella MeazzaSilvano Ferrini
Mar 22, 2013·PLoS Neglected Tropical Diseases·Corin L DorfmeierJames P McGettigan
Jul 6, 2012·Cytokine & Growth Factor Reviews·Suresh PallikkuthSavita Pahwa
Sep 8, 2010·Microbes and Infection·John S YiAllan J Zajac
Apr 6, 2017·Medical Microbiology and Immunology·Taraneh RajaeiSeyed Abdolrahim Rezaee
Mar 12, 2016·F1000Research·Warren J Leonard, Chi-Keung Wan
Jun 26, 2015·Nature Communications·Stanley AdoroLaurie H Glimcher
Jul 19, 2012·Médecine sciences : M/S·Alexandre IannelloAli Ahmad
May 12, 2017·Frontiers in Immunology·Markus GranzinEvelyn Ullrich
Sep 19, 2018·International Journal of Molecular Sciences·Yoo Jin ChoHyosun Cho
Dec 12, 2018·ACS Infectious Diseases·Nizar Mohammad AbuharfeilFawzi M Alsheyab

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