Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1-infected patients on treatment

J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):118-24. doi: 10.1097/QAI.0b013e3181fbab9f.

Abstract

PD-1 expression on T cells correlates with T-cell exhaustion and disease progression in HIV-infected patients. Previous studies have shown that combinational antiretroviral therapy induced viral suppression results in immune restoration and reduced PD-1 expression. However, a significant number of patients fail to restore CD4 T cells despite suppression of HIV replication below limit of quantification. In this study, we have analyzed PD-1 expression on CD4 and CD8 T cells in patients with poor immune reconstitution despite successful highly active antiretroviral therapy. We found that T cells of such patients express significantly higher levels of PD-1 than patients who had normal recovery of CD4 cells after treatment. In contrast, failing immune reconstitution was not associated with the expression of activation markers, indicating that PD-1 is a unique marker for failing immune reconstitution despite viral suppression. Furthermore, we show that T cells from patients with poor immune recovery differ from T cells of elderly in respect of their marker profile. PD-1 expression negatively correlated with individual CD4 cell counts, and PD-1 expressing T cells were more prone to programmed death ligand-mediated inhibition of T-cell proliferation, indicating that PD-1-mediated T-cell suppression may have a role in impaired immune reconstitution in HIV patients.

MeSH terms

  • Adult
  • Aged, 80 and over
  • Anti-HIV Agents / administration & dosage
  • Antigens, CD / analysis*
  • Apoptosis Regulatory Proteins / analysis*
  • Biomarkers / analysis*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / chemistry*
  • CD8-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor

Substances

  • Anti-HIV Agents
  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor