Programmed death-1 is a marker for abnormal distribution of naive/memory T cell subsets in HIV-1 infection

G Breton, N Chomont, H Takata… - The Journal of …, 2013 - journals.aai.org
G Breton, N Chomont, H Takata, R Fromentin, J Ahlers, A Filali-Mouhim, C Riou
The Journal of Immunology, 2013journals.aai.org
Chronic activation of T cells is a hallmark of HIV-1 infection and plays an important role in
disease progression. We previously showed that the engagement of the inhibitory receptor
programmed death (PD)-1 on HIV-1–specific CD4+ and CD8+ T cells leads to their
functional exhaustion in vitro. However, little is known about the impact of PD-1 expression
on the turnover and maturation status of T cells during the course of the disease. In this
study, we show that PD-1 is upregulated on all T cell subsets, including naive, central …
Abstract
Chronic activation of T cells is a hallmark of HIV-1 infection and plays an important role in disease progression. We previously showed that the engagement of the inhibitory receptor programmed death (PD)-1 on HIV-1–specific CD4+ and CD8+ T cells leads to their functional exhaustion in vitro. However, little is known about the impact of PD-1 expression on the turnover and maturation status of T cells during the course of the disease. In this study, we show that PD-1 is upregulated on all T cell subsets, including naive, central memory, and transitional memory T cells in HIV-1–infected subjects. PD-1 is expressed at similar levels on most CD4+ T cells during the acute and the chronic phase of disease and identifies cells that have recently entered the cell cycle. In contrast, PD-1 expression is dramatically increased in CD8+ T cells during the transition from acute to chronic infection, and this is associated with reduced levels of cell proliferation. The failure to downregulate expression of PD-1 in most T cells during chronic HIV-1 infection is associated with persistent alterations in the distribution of T cell subsets and is associated with impaired responses to IL-7. Our findings identify PD-1 as a marker for aberrant distribution of T cell subsets in HIV-1 infection.
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