Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States.
Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.
Front Immunol. 2023 Sep 18;14:1231087. doi: 10.3389/fimmu.2023.1231087. eCollection 2023.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood. Here, we found aging-associated (age ≥61) intrinsic changes in T cell responses when compared to those from individuals aged ≤ 60, even among COVID-positive patients with mild symptoms. Specifically, when stimulated with SARS-CoV-2 peptides , peripheral blood mononuclear cell (PBMC) CD4 and CD8 T cells from individuals aged ≥61 showed a diminished capacity to produce IFN-γ and IL-1β. Although they did not have severe disease, aged individuals also showed a higher frequency of PD-1 cells and significantly diminished IFN-γ/PD-1 ratios among T lymphocytes upon SARS-CoV-2 peptide stimulation. Impaired T cell IL-1β expression coincided with reduced NLRP3 levels in T lymphocytes. However, the expression of these molecules was not affected in the monocytes of individuals aged ≥61. Together, these data reveal SARS-CoV-2-specific CD4 and CD8 T-cell intrinsic cytokine alterations in the individuals older than 61 and may provide new insights into dysregulated COVID-directed immune responses in the elderly.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起 2019 年冠状病毒病（COVID-19），其临床表现从无症状或轻度感染和肺炎到与细胞因子风暴、急性呼吸窘迫综合征（ARDS）相关的严重病例，甚至死亡不等。导致这些差异的潜在机制尚不清楚，尽管已经暗示感染引起的炎症后遗症加剧与此有关。虽然高龄是已知的危险因素，但确定老年人感染 SARS-CoV-2 结局的确切免疫参数尚不清楚。在这里，我们发现与年龄≤60 岁的个体相比，年龄≥61 岁的个体的 T 细胞反应存在与衰老相关的内在变化，即使是 COVID-19 轻症患者也是如此。具体而言，用 SARS-CoV-2 肽刺激时，年龄≥61 岁的个体的外周血单核细胞（PBMC）CD4 和 CD8 T 细胞产生 IFN-γ和 IL-1β的能力减弱。尽管他们没有患重病，但老年个体在 SARS-CoV-2 肽刺激时，T 淋巴细胞中 PD-1 细胞的频率更高，IFN-γ/PD-1 比值明显降低。T 淋巴细胞中 IL-1β表达受损与 NLRP3 水平降低有关。然而，年龄≥61 岁个体的单核细胞中这些分子的表达不受影响。总之，这些数据揭示了年龄大于 61 岁的个体中 SARS-CoV-2 特异性 CD4 和 CD8 T 细胞内在细胞因子的改变，这可能为老年人 COVID 相关免疫反应失调提供新的见解。
