Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

Clin Immunol. 2019 Apr:201:55-60. doi: 10.1016/j.clim.2019.02.010. Epub 2019 Feb 26.

Abstract

Background: We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community.

Methods: Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/-). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production.

Results: CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals.

Conclusion: NK cell activation and dysfunction persisted despite seven years of suppressive ART with "normalization" of peripheral CD4 counts.

Keywords: 107a; Antiretroviral therapy; Granzyme-B; Interferon gamma; NK Cytolytic function; NK cell activation; NK cell dysfunction; NK degranulation; NKG2D; NKp46; Natural killer cells; Sub-Saharan Africa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / adverse effects*
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Black People
  • Female
  • Granzymes / immunology
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Lectins, C-Type / immunology
  • Lymphocyte Activation / drug effects
  • Lysosomal-Associated Membrane Protein 1 / immunology
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • Natural Cytotoxicity Triggering Receptor 1 / immunology
  • Phenotype

Substances

  • Anti-Retroviral Agents
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • KLRK1 protein, human
  • Lectins, C-Type
  • Lysosomal-Associated Membrane Protein 1
  • NCR1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 1
  • Granzymes