Cross-reactive CD4⁺ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8⁺ T cells. However, large numbers of memory CD8⁺ T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2–specific memory CD4⁺ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2–specific memory CD8⁺ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2–specific memory CD8⁺ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus–specific memory CD8⁺ T cells, but were functionally less potent than other virus-specific memory CD8⁺ T cell responses. The presence of preexisting tissue-resident memory CD8⁺ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

中文翻译：

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在未暴露的口咽淋巴组织中鉴定对 SARS-CoV-2 具有功能特异性的常驻记忆 CD8+ T 细胞

与 SARS-CoV -2 反应性 CD8 ⁺ T 细胞相比，在未暴露个体的外周血中更常检测到识别严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的交叉反应性 CD4 + T^细胞。然而，大量记忆 CD8 ⁺ T 细胞存在于组织中，可能具有局部 SARS-CoV-2 特异性免疫反应。为了验证这一想法，我们对扁桃体（上呼吸道的主要淋巴组织部位）中的病毒特异性 T 细胞进行了全面的功能和表型分析，并对 COVID-19 出现之前从儿童和成人中获得的外周血样本进行了匹配（2019冠状病毒病）。我们发现 SARS-CoV-2 特异性记忆 CD4 ⁺在未暴露个体的扁桃体和外周血中可以发现相似频率的 T 细胞，而功能性 SARS-CoV-2 特异性记忆 CD8 ⁺ T 细胞几乎只能在扁桃体中检测到。扁桃体 SARS-CoV-2 特异性记忆 CD8 ⁺ T 细胞表现出滤泡归巢和组织驻留记忆表型，类似于扁桃体 Epstein-Barr 病毒特异性记忆 CD8 ⁺ T 细胞，但在功能上不如其他病毒特异性记忆CD8 ⁺ T 细胞反应。未暴露个体中预先存在的组织驻留记忆 CD8 ⁺ T 细胞的存在可能会促成针对 SARS-CoV-2 的快速前哨免疫反应。