Open AccessIncreased Natural Killer Cell Activation in HIV-Infected Immunologic Non-Responders Correlates with CD4+ T Cell Recovery after Antiretroviral Therapy and Viral Suppression
Author(s) -
Zhenwu Luo,
Zhen Li,
Lisa Martin,
Zhiliang Hu,
Hao Wu,
Zhuang Wan,
Michael Kilby,
Sonya L. Heath,
Lei Huang,
Wei Jiang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0167640
Subject(s) - nkg2d , cd38 , immunology , cytotoxic t cell , interleukin 21 , t cell , cell , natural killer cell , cd8 , immune system , biology , medicine , in vitro , stem cell , microbiology and biotechnology , biochemistry , genetics , cd34
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as “immunologic responders” and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as “immunologic non-responders”. We analyzed NK cell number, subset, and activation by expression of CD107a and NKG2D and co-expression of CD38 and HLA-DR. NK cell-mediated cytotoxicity against uninfected CD4+ T cells was tested in vitro . We found that NK cell absolute number, percentage of NK cells, and percentage of NK cell subsets were similar in the three study groups. The increased NK cell activation was found predominantly in CD56dimCD16+ subset of immunologic non-responders but not immunologic responders compared to healthy controls. The activation of NK cells was inversely correlated with the peripheral CD4+ T cell count in HIV+ subjects, even after controlling for chronic T cell activation, sex, and age, potential contributors for CD4+ T cell counts in HIV disease. Interestingly, NK cells from immunologic non-responders mediated cytotoxicity against uninfected CD4+ T cells ex vivo . NK cells may play a role in blunted CD4+ T cell recovery in ART-treated HIV disease.