Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19⁺) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-γ secreting lung TRM in COVID-19⁺ and their induction in lung tissues of vaccinated COVID-19⁺. Importantly, we identify SARS-CoV-2 peptide-responding B cells and IgA⁺ plasma cells in lung tissues of COVID-19⁺ in ex vivo 3D-tissue models. Our study highlights the importance of balanced and local anti-viral immune response in the lung with persistent induction of TRM and IgA⁺ plasma cells for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.

中文翻译：

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恢复期和未感染人类受试者肺部的局部 SARS-CoV-2 肽特异性免疫反应

多特异性和持久的 T 细胞免疫已被公认为长期保护病原体的指标，包括新型冠状病毒 SARS-CoV-2，COVID-19 大流行的病原体。从 COVID-19 (COVID-19 ⁺ ) 康复的个体中外周记忆 T 细胞的功能意义开始受到重视；但对 SARS-CoV-2 感染中的肺常驻记忆 T 细胞（肺 TRM）知之甚少。在这里，我们利用灌注的三维 (3D) 人体肺组织模型，并确定肺组织中预先存在的针对 SARS-CoV-2 蛋白的局部 T 细胞免疫。我们报告了在 COVID-19 ^+中体外维持功能性多特异性 IFN-γ 分泌肺 TRM及其在接种疫苗的 COVID-19 肺组织中的诱导⁺ . 重要的是，我们在离体3D 组织模型中鉴定了 COVID-19 ⁺肺组织中的SARS-CoV-2 肽反应 B 细胞和 IgA ^{+浆细胞。}我们的研究强调了肺部平衡和局部抗病毒免疫反应的重要性，持续诱导 TRM 和 IgA ⁺浆细胞对未来预防 SARS-CoV-2 感染具有重要意义。此外，我们的数据表明，在疫苗方法中包含多种病毒抗原可能会拓宽记忆 T 细胞的功能谱，以对抗冠状病毒感染的严重程度。