Ramljak Deni, Vukoja Martina, Curlin Marina, Vukojevic Katarina, Barbaric Maja, Glamoclija Una, Purisevic Bejana, Peric Olivera, Soljic Violeta
Laboratory of Morphology, Department of Histology and Embryology, School of Medicine, University of Mostar, 88 000 Mostar, Bosnia and Herzegovina.
Health Care Center Mostar, 88 000 Mostar, Bosnia and Herzegovina.
J Pers Med. 2021 Dec 3;11(12):1291. doi: 10.3390/jpm11121291.
Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes ( = 0.007), CD3+ ( = 0.05), and CD8+ T cells ( = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) ( = 0.06) and effector memory 4 (EM4) ( < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 ( = 0.05) and lower mRNA expression of FASL ( = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 ( < 0.001) and IFN-γ ( < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK ( < 0.01) and FASL ( < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.
新冠病毒疾病（COVID-19）中健康且受控制的免疫反应对于疾病的轻症形式至关重要。尽管CD8 + T细胞在这种反应中发挥重要作用，但仍缺乏研究显示疾病初期这些细胞中的基因表达谱作为第一周后更严重疾病形式的潜在预测指标。我们研究了新冠病毒2（SARS-CoV-2）感染第一周外周血中CD8 + T细胞不同亚群的比例及其细胞毒性蛋白（穿孔素-1（PRF1）、颗粒溶素（GNLY）、颗粒酶B（GZMB）、颗粒酶A（GZMA）、颗粒酶K（GZMK））、细胞因子干扰素-γ（IFN-γ）和凋亡蛋白Fas配体（FASL）的基因表达模式。纳入了16例COVID-19患者和9名健康对照。与健康对照相比，COVID-19患者的总淋巴细胞（ = 0.007）、CD3 +（ = 0.05）和CD8 + T细胞（ = 0.01）的绝对计数显著降低。在COVID-19患者的CD8 + T细胞区室中，我们观察到效应记忆1（EM1）（ = 0.06）和效应记忆4（EM4）（ < 0.001）CD8 + T细胞的频率较低。与健康对照相比，在疾病第5天，COVID-19患者中PRF1的mRNA表达较高（ = 0.05），而FASL的mRNA表达较低（ = 0.05）。与整个病程中症状较轻的患者相比，在第一周后进展为中度和重度形式的COVID-19患者中，疾病第一周PRF1（ < 0.001）和IFN-γ（ < 0.001）的mRNA表达显著下调。与健康对照相比，所有COVID-19患者中GZMK（ < 0.01）和FASL（ < 0.01）的mRNA表达均下调。我们的结果有助于更好地理解SARS-CoV2中CD8 + T细胞不适当的免疫反应与疾病更快进展的关系。
