Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany.
Cell Rep Med. 2020 Sep 22;1(6):100092. doi: 10.1016/j.xcrm.2020.100092. Epub 2020 Aug 29.
T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4 over CD8 T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4 T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.
针对 SARS-CoV-2 刺突（S-）、膜（M-）和核衣壳（N-）蛋白的 T 细胞免疫可能决定 COVID-19 的严重程度。因此，我们比较了中度、重度和危重新冠肺炎患者与未暴露供体的 SARS-CoV-2 反应性 T 细胞反应。三种蛋白的重叠肽库诱导 SARS-CoV-2 反应性 T 细胞反应，CD4 T 细胞优于 CD8 T 细胞，并表现出针对三种蛋白的个体间免疫。M 蛋白诱导最高频率的 CD4 T 细胞，提示其对诊断和疫苗接种具有重要意义。危重新冠肺炎患者的 T 细胞反应强劲，与非危重症患者相当，甚至更强。病毒清除和 COVID-19 存活与 SARS-CoV-2 T 细胞动力学或 T 细胞反应的幅度均无关。因此，我们的数据不支持在危重新冠肺炎中存在 SARS-CoV-2 反应性免疫不足的假设。相反，这表明分化的记忆效应 T 细胞的激活可能导致危重症患者的过度反应和免疫发病机制。
