Programmed death-1 expression on CD4⁺ and CD8⁺ T cells in treated and untreated HIV disease. AIDS 2014 Jul 31;28(12):1749-58
Date
05/30/2014Pubmed ID
24871455Pubmed Central ID
PMC4206412DOI
10.1097/QAD.0000000000000314Scopus ID
2-s2.0-84904176435 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
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.
CONCLUSION: 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.
Author List
Cockerham LR, Jain V, Sinclair E, Glidden DV, Hartogenesis W, Hatano H, Hunt PW, Martin JN, Pilcher CD, Sekaly R, McCune JM, Hecht FM, Deeks SGAuthor
Leslie Cockerham MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnti-Retroviral Agents
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cohort Studies
Female
HIV Infections
Humans
Longitudinal Studies
Lymphocyte Activation
Male
Middle Aged
Programmed Cell Death 1 Receptor
Prospective Studies
RNA, Viral
Viral Load
