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
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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 Wolters Kluwer Health | Lippincott Williams & Wilkins

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