Increased early activation of CD56dimCD16dim/- natural killer cells in immunological non-responders correlates with CD4+ T-cell recovery / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 2928-2939, 2020.
Article
in English
| WPRIM
| ID: wpr-877928
ABSTRACT
BACKGROUND@#Natural killer (NK) cells play a critical role in suppressing human immunodeficiency virus-1 (HIV-1) infection, but knowledge on whether and how NK cells affect immune reconstitution in HIV-1-infected individuals who receive antiretroviral therapy (ART) is limited.@*METHODS@#We performed a case-control study with 35 healthy individuals and 66 HIV-1-infected patients including 32 immunological non-responders (INRs) with poor CD4+ T-cell recovery (500 cells/μL after 4 years of ART). NK cell phenotype, receptor repertoire, and early activation in INRs and IRs were investigated by flow cytometry.@*RESULTS@#A significantly higher proportion of CD56dimCD16dim/- NK cells was observed in INRs than IRs before ART and after 4 years of ART. The number of CD56dimCD16dim/- NK cells was inversely correlated with CD4+ T-cell counts in INRs before ART (r = -0.344, P = 0.050). The more CD69-expressing NK cells there were, the lower the CD4+ T-cell counts and ΔCD4, and these correlations were observed in INRs after ART (r = -0.416, P = 0.019; r = -0.509, P = 0.003, respectively). Additionally, CD69-expressing CD56dimCD16dim/- NK cells were more abundant in INRs than those in IRs (P = 0.018) after ART, both of which had an inverse association trend towards significance with CD4+ T-cell counts. The expression of the activating receptors NKG2C, NKG2D, and NKp46 on CD56dimCD16dim/- NK cell subsets were higher in IRs than that in INRs after 4 years of ART (all P < 0.01). Strong inverse correlations were observed between CD69 expression and NKG2C, NKG2A-NKG2C+, NKG2D, and NKp46 expression on CD56dimCD16dim/- NK cells in INRs after ART (NKG2C r = -0.491, P = 0.004; NKG2A-NKG2C+ r = -0.434, P = 0.013; NKG2D r = -0.405, P = 0.021; NKp46 r = -0.457, P = 0.008, respectively).@*CONCLUSIONS@#INRs had a larger number of CD56dimCD16dim/- NK cells characterized by higher activation levels than did IRs after ART. The increase in the CD56dimCD16dim/- NK cell subset may play an adverse role in immune reconstitution. Further functional studies of CD56dimCD16dim/- NK cells in INRs are urgently needed to inform targeted interventions to optimize immune recovery.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Killer Cells, Natural
/
CD4-Positive T-Lymphocytes
/
Case-Control Studies
/
HIV Infections
/
HIV-1
/
CD4 Lymphocyte Count
Type of study:
Observational study
/
Risk factors
Limits:
Humans
Language:
English
Journal:
Chinese Medical Journal
Year:
2020
Type:
Article
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