Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Cell Rep Med. 2022 Jun 21;3(6):100640. doi: 10.1016/j.xcrm.2022.100640. Epub 2022 May 3.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4 longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4 T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4 response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγIL-21TNF-α CD4 T cells the predominant population detected at later time points. Greater percentages of IFNγIL-21TNF-α CD4 T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4 T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4 T cells may play an important role in antibody maintenance following COVID-19.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性 CD4 T 细胞可能在对抗 2019 年冠状病毒病（COVID-19）的免疫中发挥重要作用，但我们对感染后 CD4 纵向动力学的理解以及与中和抗体维持相关的特定特征仍然有限。在这里，我们在一项由 109 名 COVID-19 门诊患者组成的纵向队列中描述了 SARS-CoV-2 特异性 CD4 T 细胞。SARS-CoV-2 特异性 CD4 反应的质量从感染后 5 天到 4 个月从产生干扰素γ（IFNγ）的细胞转变为产生肿瘤坏死因子α（TNF-α）的细胞，IFNγIL-21TNF-α CD4 T 细胞是后期检测到的主要群体。28 天时 IFNγIL-21TNF-α CD4 T 细胞的百分比与感染后 7 个月测量的 SARS-CoV-2 中和抗体呈正相关（⍴=0.4，p=0.01）。SARS-CoV-2 感染后进行 mRNA 疫苗接种可同时增强产生 IFNγ和 TNF-α的、刺突蛋白特异性 CD4 T 细胞。这些数据表明，SARS-CoV-2 特异性、产生 TNF-α的 CD4 T 细胞可能在 COVID-19 后抗体维持中发挥重要作用。
