TY - JOUR
T1 - The role of natural killer (NK) cells and nk cell receptor polymorphisms in the assessment of HIV-1 neutralization
AU - Brown, Bruce K.
AU - Wieczorek, Lindsay
AU - Kijak, Gustavo
AU - Lombardi, Kara
AU - Currier, Jeffrey
AU - Wesberry, Maggie
AU - Kappes, John C.
AU - Ngauy, Viseth
AU - Marovich, Mary
AU - Michael, Nelson
AU - Ochsenbauer, Christina
AU - Montefiori, David C.
AU - Polonis, Victoria R.
PY - 2012
Y1 - 2012
N2 - The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses.
AB - The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses.
UR - http://www.scopus.com/inward/record.url?scp=84859567727&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0029454
DO - 10.1371/journal.pone.0029454
M3 - Article
C2 - 22509241
AN - SCOPUS:84859567727
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e29454
ER -