Programmed death-1 expression on CD4⁺ and CD8⁺ T cells in treated and untreated HIV disease

AIDS. 2014 Jul 31;28(12):1749-58. doi: 10.1097/QAD.0000000000000314.

Abstract

Background: There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.

Methods: PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (≥2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n = 206).

Results: PD-1 expression levels were high on CD8⁺ T cells during early HIV infection. PD-1 levels increased on both CD4⁺ and CD8⁺ T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4⁺ T cells was associated with CD4⁺ T-cell activation (CD38⁺HLA-DR⁺) and inversely with CD4⁺ cell count. In contrast, PD-1 expression on CD8⁺ T cells was most strongly associated with CD8⁺ T-cell activation and with plasma viral load in viremic individuals.

Conclusion: Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8⁺ T-cell activation and PD-1 expression on CD8⁺ T cells. In contrast, CD4⁺ T-cell counts and CD4⁺ T-cell activation were more consistent correlates of PD-1 expression on CD4⁺ T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD8-Positive T-Lymphocytes / chemistry*
  • CD8-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / pathology*
  • Humans
  • Longitudinal Studies
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / analysis*
  • Prospective Studies
  • RNA, Viral / blood
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • RNA, Viral