Neidleman Jason, Luo Xiaoyu, George Ashley F, McGregor Matthew, Yang Junkai, Yun Cassandra, Murray Victoria, Gill Gurjot, Greene Warner C, Vasquez Joshua, Lee Sulggi, Ghosn Eliver, Lynch Kara, Roan Nadia R
Gladstone Institutes, San Francisco, CA, USA.
Department of Urology, University of California, San Francisco, CA, USA.
medRxiv. 2021 Feb 5:2021.01.22.21250054. doi: 10.1101/2021.01.22.21250054.
Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.
虽然T细胞可能在SARS-CoV-2免疫中发挥作用，但对于与重症COVID-19康复相关的SARS-CoV-2特异性T细胞的表型特征知之甚少。我们分析了34例COVID-19患者纵向样本中的T细胞，这些患者的病情严重程度从轻度（门诊患者）到最终死亡的危重症不等。相对于死亡患者，从重症COVID-19中康复的个体体内能够进行稳态增殖的SARS-CoV-2特异性T细胞数量增多且不断增加。相比之下，致命性COVID-19表现出SARS-CoV-2特异性调节性T细胞数量增加，以及被激活的旁观者CXCR4+ T细胞随时间推移而增多。再加上重症COVID-19患者肺部炎症性CXCR4+ T细胞比例增加的证明，这些结果支持了一种模型，即通过旁观者效应激活的归巢至肺部的T细胞会导致免疫病理，而强大的、非抑制性的SARS-CoV-2特异性T细胞反应则限制发病机制并促进从重症COVID-19中康复。
