title: Programmed death-1 expression on CD4⁺ and CD8⁺ T cells in treated and untreated HIV disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aHIV/AIDS Division, San Francisco General Hospital bDivision of Experimental Medicine cDepartment Epidemiology and Biostatistics, UCSF, San Francisco, California dVaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, USA.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Cockerham
authors.forename: Vivek
authors.initials: V
authors.lastname: Jain
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.forename: Wendy
authors.initials: W
authors.lastname: Hartogenesis
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.forename: Rafick
authors.initials: R
authors.lastname: Sekaly
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral