Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection
Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection
复制标题
DOI：
10.1172/jci140491
复制
发表时间：
2021-01-04
影响因子：
15.9
通讯作者：
Erdmann, Nathan
中科院分区：
文献类型：
--
作者：
Files, Jacob K.;Boppana, Sushma;Erdmann, Nathan
SARS-CoV-2引起广泛的临床表现和显著的死亡率。需要研究潜在的免疫特征，以了解疾病的发病机制和告知疫苗设计。在这项研究中，我们检查了住院和非住院个体的免疫细胞亚群。在住院患者中，许多适应性和先天性免疫细胞的频率与健康和恢复期个体相比下降，除了B淋巴细胞增加。我们的研究结果显示，住院患者中T细胞活化标志物（CD 69，OX 40，HLA-DR和CD 154）的频率增加，其他T细胞活化/耗竭标志物（PD-L1和TIGIT）在住院和非住院个体中保持升高。B细胞具有类似的活化/耗竭模式，住院期间CD 69和CD 95频率增加，随后非住院个体中PD 1频率增加。有趣的是，在非住院纵向样本中发现许多这些变化随着时间的推移而增加，这表明SARS-CoV-2感染后免疫失调的时间延长。非住院患者T细胞活化/耗竭的变化与年龄呈正相关。严重感染者的活化和耗竭标记物的表达增加。这些数据表明SARS-CoV-2感染后免疫失调的时间延长，强调需要进行更多的研究，调查恢复期个体的免疫失调。
SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase in B lymphocytes. Our findings show increased frequencies of T cell activation markers (CD69, OX40, HLA-DR, and CD154) in hospitalized patients, with other T cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization followed by an increase in PD1 frequencies in nonhospitalized individuals. Interestingly, many of these changes were found to increase overtime in nonhospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation after SARS-CoV-2 infection. Changes in T cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation after SARS-CoV-2 infection, highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.