Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.
Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.
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在HIV感染期间，病毒复制和微生物从肠道到血液的易位导致超免疫激活，这有助于HIV感染期间CD4+ T细胞数量的下降。程序性死亡-1 （PD-1）和白细胞介素-10 （IL-10）在HIV感染期间均上调。在慢性病毒感染动物模型中，阻断PD-1与程序性死亡配体-1 （PD-L1）以及IL-10与IL-10受体（IL-10R）之间的相互作用可导致病毒清除并改善T细胞功能。本研究表明，hiv感染者血浆中大量的微生物产物和炎症细胞因子导致单核细胞PD-1表达上调，这与血浆高浓度IL-10相关。通过在各种细胞类型上表达的PD-L1触发单核细胞上表达的PD-1，诱导IL-10的产生，并导致可逆的CD4+ T细胞功能障碍。我们描述了PD-1的一种新功能，即微生物产物在PD-L1结合PD-1后通过上调PD-1水平和单核细胞IL-10的产生来抑制T细胞的扩增和功能。
Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.