Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
Front Immunol. 2023 Sep 21;14:1223730. doi: 10.3389/fimmu.2023.1223730. eCollection 2023.
This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3 T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4 T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8 T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8 and CD8 T cells within the CD8 population in HD are similar, a significant increase was observed in CD8 T cell frequency in COVID-19 patients. CD8 T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8 T cells. Interestingly, the frequency of CD8 T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8/CD8 index helped to significantly improve the patient's clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8/CD8 index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.
这项工作研究了来自阿根廷科尔多瓦的患者在两次主要流行波中针对 SARS-CoV-2 的细胞免疫，这两次流行波的特点是不同的循环病毒变体和不同的社会行为。我们使用流式细胞术评估了来自住院的 COVID-19 中度和重度疾病患者的外周血中的主要淋巴细胞群体。我们的结果显示，与健康供体 (HD) 相比，细胞免疫区室存在紊乱，这在世界范围内的不同队列中都有报道。我们观察到 COVID-19 患者的 B 细胞频率增加，CD3 T 细胞频率显著降低。我们还发现 Tregs 减少，在重症患者中更为明显。在第一波中，与 HD 相比，中度和重度患者的常规 CD4 T (Tconv) 细胞中表达 GZMB、CD107a、CD39 和 PD-1 的细胞频率明显更高。在第二波中，只有中度和重度患者的 GZMB Tconv 细胞显著增加。此外，这些患者的 IL-2 产生的 Tconv 细胞频率降低。有趣的是，我们在 HD 和 COVID-19 患者中都鉴定出了两种循环 CD8 T 细胞亚群，它们具有低和高 CD8 表面表达。虽然 HD 中 CD8 群体内的 CD8 和 CD8 T 细胞的百分比相似，但 COVID-19 患者中 CD8 T 细胞的频率显著增加。HD 以及 SARS-CoV-2 感染患者的 CD8 T 细胞群体表现出较低的效应细胞因子产生细胞 TNF、IL-2 和 IFN-γ 的频率，低于 CD8 T 细胞。有趣的是，CD8 T 细胞的频率随着疾病的严重程度而增加，这表明该参数可能是疾病进展的潜在标志物。实际上，CD8/CD8 指数有助于显著改善患者的临床分层和疾病预后预测。我们的数据支持至少将 CD8/CD8 指数添加到临床实验室常用的生物标志物组中，因为其测定可能是对患者治疗管理具有影响的有用工具。
