Institut de recherche pour le developpement (IRD), Assistance-Publique Hopitaux de Marseille (APHM), Microbes Evolution Phylogénie et Infections (MEPHI), Aix-Marseille University, Marseille, France.
ImCheck Therapeutics, Marseille, France.
J Infect Dis. 2024 Jun 14;229(6):1759-1769. doi: 10.1093/infdis/jiae169.
Vγ9Vδ2 T cells play a key role in the innate immune response to viral infections through butyrophilin 3A (BTN3A). Here, we report blood Vγ9Vδ2 T cells decreased in clinically mild COVID-19 compared to healthy volunteers, and this was maintained up to 28 days and in the recovery period. Terminally differentiated Vγ9Vδ2 T cells tended to be enriched on the day of diagnosis, 28 days after, and during the recovery period. These cells showed cytotoxic and inflammatory activities following anti-BTN3A activation. BTN3A upregulation and Vγ9Vδ2 T-cell infiltration were observed in a lung biopsy from a fatal SARS-CoV-2 infection. In vitro, SARS-CoV-2 infection increased BTN3A expression in macrophages and lung cells that enhanced the anti-SARS-CoV-2 Vγ9Vδ2 T-cell cytotoxicity and interferon-γ and tumor necrosis factor-α. Increasing concentrations of anti-BTN3A lead to viral replication inhibition. Altogether, we report Vγ9Vδ2 T cells are important in the immune response against SARS-CoV-2 infection and activation by anti-BTN3A antibody may enhance their response. Clinical Trials Registration. NCT04816760.
γ9δ2 T 细胞通过对丁酰膦酰基 3A（BTN3A）的反应在病毒感染的先天免疫中发挥关键作用。在这里，我们报告了与健康志愿者相比，临床上轻度 COVID-19 患者血液中的γ9δ2 T 细胞减少，这种情况持续到 28 天及恢复期。终末分化的γ9δ2 T 细胞在诊断当天、28 天后和恢复期趋于富集。这些细胞在抗 BTN3A 激活后表现出细胞毒性和炎症活性。在一例致命性 SARS-CoV-2 感染的肺活检中观察到 BTN3A 上调和γ9δ2 T 细胞浸润。在体外，SARS-CoV-2 感染增加了巨噬细胞和肺细胞中的 BTN3A 表达，增强了抗 SARS-CoV-2 γ9δ2 T 细胞的细胞毒性和干扰素-γ 和肿瘤坏死因子-α。增加的抗 BTN3A 浓度导致病毒复制抑制。总的来说，我们报告 γ9δ2 T 细胞在针对 SARS-CoV-2 感染的免疫反应中很重要，并且抗 BTN3A 抗体的激活可能增强其反应。临床试验注册。NCT04816760。
