Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China; Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Autoimmun Rev. 2023 Sep;22(9):103392. doi: 10.1016/j.autrev.2023.103392. Epub 2023 Jul 15.
The evolutionary emergence of adaptive immunity has significantly extended the lifespan of humans and other species. The adaptive immune system is essential for host survival and adaptation to the rapidly changing environment of potential pathogens; however, it also leads to self-antigen recognition that creates the risk of autoimmune disease. Although this mechanism is generally acknowledged, it is difficult to trace back to the initial causative event of pathogen infection that occurs long before the clinical onset of autoimmune disease. The recognitions of foreign-and self-antigens are faithfully registered by the individual's immune repertoire. In this study, through interrogating 1414 T-cell repertoires collected during the COVID-19 pandemic, we sought to trace the immunological host defense against COVID-19 infection, while investigating whether such disturbance of T-cell repertoire will lead to auto-reactive T cells. The percentages of ankylosing spondylitis-specific T cells were significantly increased with increasing COVID-19-specific T cells (p < 0.0001, rho = 0.38). This finding implies T cell cross-reactivity that leads to a plausible trade-off between the benefit of immunological host defense and the risk of autoimmune disease. As such, given that the immunological host defense serves as the top priority for improving host survival, the adaptive immune system may need to adapt to deadly threats at the expense of autoimmune diseases, most of which do not affect host reproduction and survival. This finding has important implications for the primary prevention of autoimmune disease and the vaccine design strategy for COVID-19. Moreover, this study provides a feasible workflow to profile the probability of T cell cross-reactivity and extrapolates the findings of autoimmune imprinting from bench to bedside.
适应性免疫的进化出现极大地延长了人类和其他物种的寿命。适应性免疫系统对于宿主的生存和适应潜在病原体不断变化的环境至关重要；然而，它也导致了自身抗原的识别，从而增加了自身免疫性疾病的风险。尽管这一机制已被普遍认可，但很难追溯到自身免疫性疾病临床发病前很久就发生的病原体感染的最初致病事件。个体的免疫库忠实地记录了对外源和自身抗原的识别。在这项研究中，我们通过分析在 COVID-19 大流行期间收集的 1414 个 T 细胞库，旨在追踪针对 COVID-19 感染的免疫宿主防御，同时研究这种 T 细胞库的干扰是否会导致自身反应性 T 细胞。随着 COVID-19 特异性 T 细胞的增加，强直性脊柱炎特异性 T 细胞的百分比显著增加（p<0.0001，rho=0.38）。这一发现意味着 T 细胞交叉反应，这可能导致免疫宿主防御的益处和自身免疫性疾病的风险之间的权衡。因此，鉴于免疫宿主防御是提高宿主生存的首要任务，适应性免疫系统可能需要以牺牲自身免疫性疾病为代价来适应致命威胁，而大多数自身免疫性疾病不会影响宿主的繁殖和生存。这一发现对自身免疫性疾病的一级预防和 COVID-19 的疫苗设计策略具有重要意义。此外，本研究提供了一种可行的工作流程来分析 T 细胞交叉反应的可能性，并将自身免疫印迹的研究结果从实验室扩展到临床。
