Programmed death 1 receptor changes ex vivo in HIV-infected adults following initiation of highly active antiretroviral therapy

Clin Vaccine Immunol. 2012 May;19(5):752-6. doi: 10.1128/CVI.00093-12. Epub 2012 Mar 21.


This study investigates the short-term effects of highly active antiretroviral therapy (HAART) on programmed death 1 receptor (PD-1) expression and lymphocyte function. We compared lymphocytes from human immunodeficiency virus (HIV)-infected adults prior to the initiation of HAART with lymphocytes from the same subjects following 2 months of treatment. Short-term HAART resulted in a moderate increase in the expression of PD-1 on both CD4(+) and CD8(+) T cells; yet, there was still a significant reduction in viral load and recovery of CD4(+) T cells. After 2 months of HAART, lymphocytes from the subjects had a reduction in lymphoproliferative responses to phytohemagglutinin (PHA) and an increased response to the Candida recall antigen and the HIV antigen p24 compared to pretreatment lymphocytes. PHA-stimulated peripheral blood mononuclear cells (PBMCs) from samples obtained 2 months after HAART produced higher levels of Th-1 cytokines (gamma interferon [IFN-γ] and tumor necrosis factor alpha[TNF-α]) than the levels observed for samples taken before treatment was initiated. There were no significant changes in the proinflammatory cytokine interleukin-2 (IL-2) or Th-2 cytokines (IL-4, IL-5, and IL-10) in the corresponding samples. Ex vivo PD-1 blockade significantly augmented PHA-induced lymphoproliferation as well as the levels of Th-1 cytokines and to a lesser extent the levels of Th-2 cytokines in PBMC cultures. The ability to downregulate PD-1 expression may be important in enhancing immune recovery in HIV infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • Antigens, Fungal / immunology
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Candida / immunology
  • Cell Proliferation
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Viral Load


  • Anti-Retroviral Agents
  • Antigens, Fungal
  • Programmed Cell Death 1 Receptor