Division of Immunology and Allergic Diseases, Department of Chest Diseases, Ankara Yıldırım Beyazıt University Faculty of Medicine, Ankara, Türkiye.
Clinic of Immunology and Allergic Diseases, Ankara Bilkent City Hospital, Ankara, Türkiye.
Tuberk Toraks. 2024 Jun;72(2):152-166. doi: 10.5578/tt.202402929.
: Immune responses against Coronavirus (SARS-CoV-2) may be highly complex. It has been suggested that T-cell fatigue develops due to continuous stimulation of T-cells by SARS-CoV-2 in Coronavirus disease-2019 (COVID-19). It was aimed to assess peripheral lymphocyte subsets and T-cell exhaustion in various clinical courses of the disease in patients diagnosed with COVID-19.
This study included 150 patients who were assigned into the "mild-to-moderate disease" group, or "severe disease" group based on their clinical and laboratory characteristics. Peripheral lymphocyte subsets and T-cell exhaustion markers [programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)] were determined in the peripheral blood using flow cytometry.
Mean (±SD) age was 53.3 ± 14.5 years, and female to male ratio was 55/95. In the mild-to-moderate disease (MMD) group, 55 patients had pneumonia and 20 patients had COVID-19 without pneumonia. In the severe disease (SD) group, 43 patients had severe pneumoniae and 32 patients were in critical condition. Lymphocyte counts were less than 1.0 x 109/L in 69.3% of the patients in the SD group, and the difference between the MMD group and SD group was statistically significant (p= 0.001). Total T cells, CD4+ and CD8+ T-cell counts were significantly lower in the SD group vs. MMD group (p< 0.001, p< 0.001, p< 0.001, respectively). PD-1 expression by CD8+ and CD4 T+ cells was higher (p= 0.042, p= 0.029, respectively) and Tim-3 expression from CD4 T+ cells was lower (p= 0.000) in the SD group vs. MMD group. Serum IFN-γ levels were not statistically different in the MMD and SD groups (p= 0.2).
T-cell counts may be significantly reduced along with an increased expression of the T-cell exhaustion marker PD-1 in severe COVID-19, but Tim-3 expression was not increased in our study patients.
针对冠状病毒（SARS-CoV-2）的免疫反应可能非常复杂。有人提出，由于 SARS-CoV-2 在 2019 年冠状病毒病（COVID-19）中持续刺激 T 细胞，因此会出现 T 细胞疲劳。本研究旨在评估 COVID-19 患者不同临床病程中外周淋巴细胞亚群和 T 细胞耗竭的情况。
本研究纳入了 150 名患者，根据其临床和实验室特征分为“轻症-中度疾病”组或“重症疾病”组。采用流式细胞术检测外周血中淋巴细胞亚群和 T 细胞耗竭标志物[程序性死亡蛋白 1（PD-1）和 T 细胞免疫球蛋白和粘蛋白结构域 3（Tim-3）]。
患者平均（±SD）年龄为 53.3±14.5 岁，男女比例为 55/95。在轻症-中度疾病（MMD）组中，55 例患者患有肺炎，20 例患者患有无肺炎的 COVID-19。在重症疾病（SD）组中，43 例患者患有严重肺炎，32 例患者病情危急。SD 组中 69.3%的患者淋巴细胞计数<1.0×109/L，MMD 组与 SD 组之间的差异具有统计学意义（p=0.001）。SD 组总 T 细胞、CD4+和 CD8+T 细胞计数明显低于 MMD 组（p<0.001，p<0.001，p<0.001）。与 MMD 组相比，SD 组 CD8+和 CD4+T 细胞 PD-1 表达更高（p=0.042，p=0.029），CD4+T 细胞 Tim-3 表达更低（p=0.000）。MMD 和 SD 组血清 IFN-γ水平无统计学差异（p=0.2）。
严重 COVID-19 患者的 T 细胞计数可能明显减少，同时 T 细胞耗竭标志物 PD-1 的表达增加，但在本研究患者中 Tim-3 表达未增加。
