Robust interferon-α and IL-12 responses by dendritic cells are related to efficient CD4+ T-cell recovery in HIV patients on ART

Clin Immunol. 2011 May;139(2):115-21. doi: 10.1016/j.clim.2011.02.015. Epub 2011 Feb 23.

Abstract

Amongst HIV patients with successful virological responses to antiretroviral therapy (ART), poor CD4(+) T-cell recovery is associated with low nadir CD4(+) T-cell counts and persistent immune activation. These factors might be influenced by dendritic cell (DC) function. Interferon-α-producing plasmacytoid DC and IL-12-producing myeloid DC were quantified by flow cytometry after stimulation with agonists to TLR7/8 (CL075) or TLR9 (CpG-ODN). These were compared between patients who achieved CD4(+) T-cell counts above or below 200 cells/μL after 6 months on ART (High vs. Low groups). High Group patients had more DC producing interferon-α or IL-12 at Weeks 6 and 12 on ART than Low Group patients. The frequencies of cytokine-producing DC at Week 12 were directly correlated with CD4(+) T-cell counts at baseline and at Week 12. Patients with good recovery of CD4(+) T-cells had robust TLR-mediated interferon-α responses by plasmacytoid DC and IL-12 responses by myeloid DC during early ART (1-3 months).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • HIV Infections / drug therapy*
  • HIV Infections / pathology*
  • HLA-DR Antigens / metabolism
  • Humans
  • Interferon-alpha / metabolism*
  • Interleukin-12 / metabolism*
  • Leukocyte Count
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Oligodeoxyribonucleotides / pharmacology
  • Quinolines / pharmacology
  • Thiazoles / pharmacology
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 8 / agonists
  • Toll-Like Receptor 9 / agonists

Substances

  • Anti-Retroviral Agents
  • CL 075
  • CPG-oligonucleotide
  • HLA-DR Antigens
  • Interferon-alpha
  • Membrane Glycoproteins
  • Oligodeoxyribonucleotides
  • Quinolines
  • TLR7 protein, human
  • TLR8 protein, human
  • TLR9 protein, human
  • Thiazoles
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Interleukin-12
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1