AIDS

Skip Navigation LinksHome > July 31, 2014 - Volume 28 - Issue 12 > Programmed death-1 expression on CD4+ and CD8+ T cells in tr...
AIDS:
doi: 10.1097/QAD.0000000000000314
Clinical Science

Programmed death-1 expression on CD4+ and CD8+ T cells in treated and untreated HIV disease

Cockerham, Leslie R.a; Jain, Viveka; Sinclair, Elizabethb; Glidden, David V.c; Hartogenesis, Wendya; Hatano, Hiroyua; Hunt, Peter W.a; Martin, Jeffrey N.c; Pilcher, Christopher D.a; Sekaly, Rafickd; McCune, Joseph M.b; Hecht, Frederick M.a; Deeks, Steven G.a

Supplemental Author Material
Collapse Box

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.

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.

© 2014 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.