美国埃默里大学Mirko Paiardini团队揭示，淋巴结中不同猿免疫缺陷病毒（SIV）特异性的CD8⁺ T细胞，同时表现出效应细胞和干细胞特征并与SIV持久性有关。2024年6月17日出版的《自然-免疫学》发表了这项成果。

据悉，越来越多地研究利用CD8⁺ T细胞来治疗人类免疫缺陷病毒，这需要更深入地了解参与控制HIV的CD8⁺ T细胞。

研究人员发现了一个抗原反应性TOX^hiTCF1⁺CD39⁺CD8⁺ T细胞群，其高表达抑制性受体且低表达典型细胞溶解分子。通过对SIV特异性CD8⁺ T细胞转录分析和CD8⁺ T细胞亚群的蛋白质组学分析，研究确定了TOX^hiTCF1⁺CD39⁺CD8⁺ T细胞是中间效应细胞，它们保留了干细胞样特征，与最终效应T细胞有种系关系。在滤泡微环境中，TOX^hiTCF1⁺CD39⁺CD8⁺ T细胞的出现频率高于TCF1-CD39⁺CD8⁺ T细胞，并优先位于SIV-RNA⁺细胞附近。

它们的出现频率与血浆病毒血症减少和SIV储库规模降低有关。在未接受抗逆转录病毒治疗的人类免疫缺陷病毒（HIV）感染者，和携带HIV病毒的抗逆转录病毒治疗抑制者的淋巴结中，检测到了高度相似的TOX^hiTCF1⁺CD39⁺CD8⁺ T细胞，这表明这群CD8⁺ T细胞有助于限制SIV和HIV的持续存在。

附：英文原文

Title: Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence

Author: Strongin, Zachary, Raymond Marchand, Laurence, Deleage, Claire, Pampena, M. Betina, Cardenas, Maria Andrea, Beusch, Christian Michel, Hoang, Timothy N., Urban, Elizabeth A., Gourves, Mael, Nguyen, Kevin, Tharp, Gregory K., Lapp, Stacey, Rahmberg, Andrew R., Harper, Justin, del Rio Estrada, Perla M., Gonzalez-Navarro, Mauricio, Torres-Ruiz, Fernanda, Luna-Villalobos, Yara Andrea, Avila-Rios, Santiago, Reyes-Teran, Gustavo, Sekaly, Rafick, Silvestri, Guido, Kulpa, Deanna A., Saez-Cirion, Asier, Brenchley, Jason M., Bosinger, Steven E., Gordon, David Ezra, Betts, Michael R., Kissick, Haydn T., Paiardini, Mirko

Issue&Volume: 2024-06-17

Abstract: Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+ T cell functions, which requires a deeper understanding of CD8+ T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+ T cells and proteomic analysis of purified CD8+ T cell subsets identified TOXhiTCF1+CD39+CD8+ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+ T cells were found at higher frequency than TCF1CD39+CD8+ T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+ cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+ T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+ T cells contributes to limiting SIV and HIV persistence.

DOI: 10.1038/s41590-024-01875-0

Source: https://www.nature.com/articles/s41590-024-01875-0