Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Saint-Luc, Montreal, Quebec H2X 1P1, Canada.
J Immunol. 2013 Sep 1;191(5):2194-204. doi: 10.4049/jimmunol.1200646. Epub 2013 Aug 5.
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.
慢性 T 细胞激活是 HIV-1 感染的标志，在疾病进展中起着重要作用。我们之前曾表明，HIV-1 特异性 CD4(+)和 CD8(+)T 细胞上抑制性受体程序性死亡（PD）-1 的结合导致它们在体外功能衰竭。然而，对于 PD-1 表达对疾病过程中 T 细胞的周转率和成熟状态的影响知之甚少。在这项研究中，我们表明 PD-1 在所有 T 细胞亚群（包括 HIV-1 感染受试者中的幼稚、中央记忆和过渡记忆 T 细胞）上均上调。在疾病的急性和慢性阶段，PD-1 在大多数 CD4(+)T 细胞上的表达水平相似，并识别最近进入细胞周期的细胞。相比之下，PD-1 在 CD8(+)T 细胞中的表达在从急性到慢性感染的转变过程中显著增加，这与细胞增殖水平降低有关。在慢性 HIV-1 感染期间，大多数 T 细胞中 PD-1 的表达未能下调与 T 细胞亚群分布的持续改变有关，并与 IL-7 反应受损有关。我们的研究结果将 PD-1 确定为 HIV-1 感染中 T 细胞亚群异常分布的标志物。
