Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Department of Biology, Johns Hopkins University, Baltimore, MD, United States.
Front Immunol. 2020 Dec 21;11:600405. doi: 10.3389/fimmu.2020.600405. eCollection 2020.
Aberrant T cell differentiation and lymphopenia are hallmarks of severe COVID-19 disease. Since T cells must race to cull infected cells, they are quick to differentiate and achieve cytotoxic function. With this responsiveness, comes hastened apoptosis, due to a coupled mechanism of death and differentiation in both CD4+ and CD8+ lymphocytes CD95 (Fas) and serine-threonine kinase (Akt). T cell lymphopenia in severe cases may represent cell death or peripheral migration. These facets depict SARS-Cov-2 as a lympho-manipulative pathogen; it distorts T cell function, numbers, and death, and creates a dysfunctional immune response. Whether preservation of T cells, prevention of their aberrant differentiation, and expansion of their population may alter disease course is unknown. Its investigation requires experimental interrogation of the linked differentiation and death pathway by agents known to uncouple T cell proliferation and differentiation in both CD4+ and CD8+ T cells.
异常的 T 细胞分化和淋巴细胞减少是严重 COVID-19 疾病的特征。由于 T 细胞必须迅速清除感染细胞，因此它们会迅速分化并获得细胞毒性功能。这种反应性导致 CD4+和 CD8+淋巴细胞中死亡和分化的偶联机制导致细胞凋亡加速，CD95（Fas）和丝氨酸苏氨酸激酶（Akt）。严重病例中的 T 细胞淋巴细胞减少可能代表细胞死亡或外周迁移。这些方面表明 SARS-CoV-2 是一种淋巴操纵病原体；它扭曲了 T 细胞的功能、数量和死亡，并导致免疫功能障碍。保存 T 细胞、防止其异常分化以及扩大其数量是否可能改变疾病进程尚不清楚。需要通过已知可分离 CD4+和 CD8+T 细胞增殖和分化的试剂来实验性探究相关的分化和死亡途径，以对此进行研究。
