Th1 and Th17 proinflammatory profile characterizes invariant natural killer T cells in virologically suppressed HIV+ patients with low CD4+/CD8+ ratio

AIDS. 2016 Nov 13;30(17):2599-2610. doi: 10.1097/QAD.0000000000001247.

Abstract

Introduction: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients.

Methods: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR).

Results: Patients with low ratio had lower percentage of CD4 iNKT cells compared with patients with high ratio and higher CD8 iNKT cell percentage; double-negative iNKT cells were lower in HIV+ patients compared with CTR. Patients with low ratio had higher percentage of CD4 and double-negative iNKT cells expressing CD38 and HLA-DR compared with patients with high ratio. CD4 iNKT cells expressing PD-1 were higher in patients with CD4/CD8 ratio less than 0.4, whereas double-negative iNKT cells expressing PD-1 were lower compared with patients with ratio more than 1.1. Patients with low ratio had higher CD4 iNKT cells producing IL-17, CD8 iNKT cells producing IFN-γ, TNF-α or IFN-γ and TNF-α, and double-negative iNKT cells producing IL-17 or IL-17 and IFN-γ compared with CTR. Activated CD4 (or CD8) T cells correlated with activated CD4 (or CD8) iNKT cells, as well as the percentages of CD4 (or CD8) T cells expressing PD-1 was correlated to that of CD4 (or CD8) iNKT cells expressing PD-1.

Conclusion: Low CD4/CD8 ratio despite effective combined antiretroviral therapy is associated with altered iNKT cell subsets, enhanced activation, and prominent Th1/Th17 proinflammatory profile.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • CD4-CD8 Ratio*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • HIV Infections / pathology*
  • Humans
  • Male
  • Middle Aged
  • Natural Killer T-Cells / immunology*
  • Sustained Virologic Response
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • Anti-Retroviral Agents