There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human T cell recall responses to fully glycosylated spike trimer, recombinant N protein, as well as to S, N, M, and E peptide pools in the early convalescent phase and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2-specific T cell responses to at least one Ag. Both SARS-CoV-2-specific and influenza-specific CD4+ T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2-specific CD4+ T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. Most SARS-CoV-2-convalescent subjects also produced IFN-γ in response to seasonal OC43 S protein. We observed granzyme B+/IFN-γ+, CD4+, and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ T cell responses predominating over CD8+ T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain-specific IgA; however, the frequency of pTfh responses to SARS-CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4+ Th1 responses predominate over CD8+ T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease.

中文翻译：

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系统检查抗原特异性回忆 T 细胞对 SARS-CoV-2 与流感病毒的反应，揭示了独特的炎症特征

迫切需要深入了解 SARS-CoV-2 的免疫力。在这项研究中，我们研究了恢复期早期人类 T 细胞对完全糖基化刺突三聚体、重组 N 蛋白以及 S、N、M 和 E 肽池的记忆反应，并将其与流感特异性记忆反应进行比较。相同的捐助者。所有受试者均表现出对至少一种 Ag 的 SARS-CoV-2 特异性 T 细胞反应。SARS-CoV-2 特异性和流感特异性 CD4+ T 细胞反应主要是中枢记忆表型；然而，与来自同一供体的流感特异性记忆反应相比，SARS-CoV-2 特异性 CD4+ T 细胞表现出较低的 IFN-γ 与 TNF 比率，与疾病严重程度无关。SARS-CoV-2 特异性 T 细胞的多功能性低于流感特异性 T 细胞，尤其是在严重病例中，这可能表明其已经衰竭。大多数 SARS-CoV-2 恢复期受试者也会因季节性 OC43 S 蛋白而产生 IFN-γ。我们在大多数个体中观察到颗粒酶 B+/IFN-γ+、CD4+ 和 CD8+ 对肽池的增殖反应，其中 CD4+ T 细胞反应优于 CD8+ T 细胞反应。外周滤泡辅助 T (pTfh) 对 S 或 N 的反应与血清中和测定以及受体结合域特异性 IgA 密切相关；然而，pTfh 对 SARS-CoV-2 的反应频率低于 pTfh 对流感病毒的反应频率。总体而言，T 细胞对 SARS-CoV-2 的反应很强；然而，在同一供体中，CD4+ Th1 反应比 CD8+ T 细胞反应占主导地位，炎症特征更强，pTfh 反应比流感病毒反应更弱，可能导致 COVID-19 疾病。