Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers
Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers
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DOI：
10.1097/qad.0000000000003013
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发表时间：
2021-11-15
期刊：
影响因子：
3.8
通讯作者：
Yamamoto，Hiroyuki
中科院分区：
文献类型：
--
作者：
Kanno，Yoshiaki;Hau，Trang Thi Thu;Yamamoto，Hiroyuki
目的：分析表位特异性CD8+ t细胞反应的数量和质量对了解HIV/猴免疫缺陷病毒（SIV）复制控制机制至关重要。我们之前的研究表明，急性期被动输注中和抗体（nab）可增强恒河猴的广泛t细胞反应和强大的SIV mac239控制。分析这些SIV控制者的CD8+ t细胞反应的长期动态为设计持久的抗hiv免疫提供了重要的见解。设计：我们分析了急性期被动NAb输注控制SIV mac239复制的恒河猴SIV特异性CD8+ t细胞反应的动力学和代谢/功能特征。方法：观察4例被动nab输注SIV控制者在多个慢性期时间点的外周血表位特异性CD8+ t细胞反应。特别地，我们检测了Eomes （Eomes）、磷酸化AMP激酶（pAMPK）、CD28和程序性死亡-1 （PD-1）的表达模式。结果：在注射了nab的SIV控制者中，在急性感染中检测到的单表位特异性CD8+ t细胞反应维持在低水平，直到1年后，直到2年后出现激增。在这些表位特异性CD8+ T细胞中，效应因子偏转和未耗尽的eomes -高/ pampk -低/ cd28 -阴性/ pd -1-低亚群的保留与它们在残余病毒复制控制中的前线承诺有关。结论：在急性期被动NAb输注后的长期SIV控制中，在慢性期主要诱导单表位、高质量的CTL反应。这些结果可能描述了免疫显性表位特异性CD8+ t细胞保存的一种有利模式，并表明结合代谢标记对于理解基于NAb/ t细胞协同作用的HIV/SIV控制的重要性。
Objective:Analysis of the quantity and quality of epitope-specific CD8+ T-cell responses is crucial for understanding the mechanism of HIV/simian immunodeficiency virus (SIV) replication control. We have previously shown that acute-phase passive infusion of neutralizing antibodies (NAbs) results in augmented broad T-cell responses and robust SIV mac239 control in rhesus macaques. Analyzing long-term dynamics of CD8+ T-cell responses in these SIV controllers provides important insights into designing lasting anti-HIV immunity.Design:We analyzed dynamics and metabolic/functional profiles of SIV-specific CD8+ T-cell responses in rhesus macaques that controlled SIV mac239 replication following acute-phase passive NAb infusion.Methods:SIV epitope-specific CD8+ T-cell responses in peripheral blood at multiple chronic-phase time points were investigated in four passive NAb-infused SIV controllers. In particular, expression patterns of Eomesodermin (Eomes), phosphorylated AMP kinase (pAMPK), CD28 and programmed death-1 (PD-1) were examined.Results:In the NAb-infused SIV controllers, a single epitope-specific CD8+ T-cell response detected from acute infection and maintaining low levels up to year 1 showed a surge thereafter, up to year 2 postchallenge. Retention of an effector-skewed and unexhausted Eomes-high/pAMPK-low/CD28-negative/PD-1-low subpopulation in these epitope-specific CD8+ T cells implicated their front-line commitment in residual viral replication control.Conclusion:In long-term SIV control following acute-phase passive NAb infusion, a single-epitope, high-quality CTL response was dominantly induced in the chronic phase. These results likely describe one favorable pattern of immunodominant epitope-specific CD8+ T-cell preservation and suggest the importance of incorporating metabolic marker signatures for understanding NAb/T-cell synergism-based HIV/SIV control.