TY - JOUR
T1 - Programmed death-1 is a marker for abnormal distribution of naive/memory T cell subsets in HIV-1 infection
AU - Breton, Gaëlle
AU - Chomont, Nicolas
AU - Takata, Hiroshi
AU - Fromentin, Rémi
AU - Ahlers, Jeffrey
AU - Filali-Mouhim, Abdelali
AU - Riou, Catherine
AU - Boulassel, Mohamed Rachid
AU - Routy, Jean Pierre
AU - Yassine-Diab, Bader
AU - Sékaly, Rafick Pierre
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.1200646
DO - 10.4049/jimmunol.1200646
M3 - Article
C2 - 23918986
AN - SCOPUS:84883354823
SN - 0022-1767
VL - 191
SP - 2194
EP - 2204
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -