Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, Poland.
Outpatient Clinic, Warsaw Hospital for Infectious Diseases, 01-201 Warsaw, Poland.
Cells. 2023 May 22;12(10):1446. doi: 10.3390/cells12101446.
In chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4CD8) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells, including HCV-specific cells, and assessed the effect of successful HCV treatment on inhibitory receptors expression. Blood samples from 97 CHC patients were collected before and six months post-treatment. PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) expression was assessed by flow cytometry. DP T-cells displayed significantly higher PD-1 expression, lower Tim-3 expression than CD8 SP T-cells and lower percentages of PD-1Tim-3 cells than CD4 SP T-cells, both before and after treatment. PD-1Tim-3 DP T-cells decreased following treatment. HCV-specific cells were more frequent among DP than SP T-cells, both before and after treatment. HCV-specific DP T-cells were characterized by lower PD-1 expression, higher PD-1 and Tim-3 co-expression, and lower percentages of PD-1Tim-3 cells (both before and after treatment) and higher post-treatment Tim-3 than HCV-specific SP T-cells. Their percentages decreased following treatment, but the exhaustion phenotype remained unchanged. DP T-cells in CHC exhibit a distinct exhaustion phenotype from SP T-cells, and these changes mostly persist following successful treatment.
在慢性丙型肝炎（CHC）中，T 细胞功能衰竭，外周血中双阳性（DP）（CD4CD8）细胞的频率增加。我们比较了 DP 和单阳性（SP）T 细胞之间的衰竭表型，包括 HCV 特异性细胞，并评估了成功 HCV 治疗对抑制性受体表达的影响。采集了 97 例 CHC 患者治疗前和治疗后 6 个月的血液样本。通过流式细胞术评估 PD-1（程序性细胞死亡蛋白 1）和 Tim-3（T 细胞免疫球蛋白和粘蛋白结构域分子 3）的表达。DP T 细胞的 PD-1 表达显著高于 CD8 SP T 细胞，Tim-3 表达显著低于 CD4 SP T 细胞，治疗前后 PD-1Tim-3 DP T 细胞的比例均低于 CD4 SP T 细胞。治疗后 PD-1Tim-3 DP T 细胞减少。治疗前后 DP T 细胞中 HCV 特异性细胞的频率均高于 SP T 细胞。HCV 特异性 DP T 细胞的 PD-1 表达较低，PD-1 和 Tim-3 共表达较高，PD-1Tim-3 DP T 细胞的比例较低（治疗前后），治疗后 Tim-3 高于 HCV 特异性 SP T 细胞。它们的比例在治疗后下降，但衰竭表型保持不变。CHC 中的 DP T 细胞表现出与 SP T 细胞不同的衰竭表型，并且这些变化在成功治疗后大多持续存在。
