TY - JOUR
T1 - IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication
AU - Iannello, Alexandre
AU - Boulassel, Mohamed Rachid
AU - Samarani, Suzanne
AU - Tremblay, Cécile
AU - Toma, Emil
AU - Routy, Jean Pierre
AU - Ahmad, Ali
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - LFA-1
KW - MAPK
KW - Perforin
KW - STAT-3
UR - http://www.scopus.com/inward/record.url?scp=77952540913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952540913&partnerID=8YFLogxK
U2 - 10.1189/jlb.1009701
DO - 10.1189/jlb.1009701
M3 - Article
C2 - 20103765
AN - SCOPUS:77952540913
SN - 0741-5400
VL - 87
SP - 857
EP - 867
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -