Abstract
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.
Highlights
Antiretroviral therapy (ART) dramatically suppresses HIV viral replication, improves immune function, restores CD4+ T cells, increases survival, and delays disease progression in HIV disease [1,2,3]
To further determine natural killer (NK) cell activation in HIV+ subjects with different degrees of immune restoration after long-term ART treatment and viral suppression, we analyzed the expression of CD38, HLA-DR, CD107a, and NKG2D on NK cells in the current study
If HIV+ subjects were stratified into immunologic responders and non-responders, the non-responders had significant higher frequency of CD38 and HLA-DR co-expression compared to responders and healthy controls (Fig 2A and 2B)
Summary
Antiretroviral therapy (ART) dramatically suppresses HIV viral replication, improves immune function, restores CD4+ T cells, increases survival, and delays disease progression in HIV disease [1,2,3]. Up to 25% patients fail to reconstitute their CD4+ T cells to the levels similar to healthy controls despite HIV suppression under ART treatment [2, 4, 5]. Inflammatory syndrome, heightened morbidity and mortality, are seen in persons who fail to increase their CD4 + T cell counts under ART treatment [3, 6,7,8,9,10]. Chronic T cell activation is a predictive marker for peripheral CD4+ T cell count and disease progression in HIV disease [24,25,26]. The magnitude of T cell activation in this setting is associated with the degrees of CD4+ T cell recovery [29]
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