Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Cell. 2020 Nov 12;183(4):996-1012.e19. doi: 10.1016/j.cell.2020.09.038. Epub 2020 Sep 16.
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4 and CD8 T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4 and CD8 T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4 and CD8 T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4 T cell, CD8 T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.
关于抗原特异性免疫反应与 COVID-19 疾病严重程度之间的关系，目前所知有限。我们在急性和恢复期患者中完成了对适应性免疫三个分支的综合检查，包括 SARS-CoV-2 特异性 CD4 和 CD8 T 细胞以及中和抗体反应。SARS-CoV-2 特异性 CD4 和 CD8 T 细胞均与疾病较轻相关。协调的 SARS-CoV-2 特异性适应性免疫反应与疾病较轻相关，表明 CD4 和 CD8 T 细胞在 COVID-19 的保护性免疫中均发挥作用。值得注意的是，≥65 岁的个体中 SARS-CoV-2 抗原特异性反应的协调性被破坏。幼稚 T 细胞的缺乏也与衰老和不良疾病结局相关。一个简单的解释是，协调的 CD4 T 细胞、CD8 T 细胞和抗体反应具有保护作用，但不协调的反应常常无法控制疾病，衰老与 SARS-CoV-2 的适应性免疫反应受损之间存在联系。
