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. 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.

SUBMITTER: Cockerham LR 

PROVIDER: S-EPMC4206412 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature