title: Programmed death 1 receptor changes ex vivo in HIV-infected adults following initiation of highly active antiretroviral therapy.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Spitsin
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Tustin
authors.forename: Eric
authors.initials: E
authors.lastname: Riedel
authors.forename: Richard
authors.initials: R
authors.lastname: Tustin
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Murray
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Peck
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khan
authors.forename: Joseph
authors.initials: J
authors.lastname: Quinn
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D000946:Antigens, Fungal / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002175:Candida / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000946:Antigens, Fungal; D061026:Programmed Cell Death 1 Receptor