CD226 and the inhibitory T-cell immunoglobulin and ITIM domain (TIGIT) belong to a co-stimulatory receptor system found in both T and natural killer cells. Although data from genome-wide studies have suggested a strong association between the CD226 locus and multiple autoimmune diseases, the understanding of the balance of CD226/TIGIT axis during the activation of human T-cell subpopulation remains incomplete. In this study, we aimed to compare pre- and post-stimulation expression profiles of CD226 and TIGIT with those of CD28 in human CD4⁺ and CD8⁺ T-cell subpopulations using flow cytometry. The impact of the CD226 single nucleotide polymorphism, rs763361, on cell surface CD226 expression and effector cytokine secretion was also examined. Peripheral blood mononuclear cells from healthy blood donors (n = 65) were studied. Most naïve CD4⁺ and CD8⁺ T-cells did not express CD226 and TIGIT, predominantly upregulating activating receptors following stimulation. Memory CD4⁺ T-cells exhibited a balanced expression of activating and inhibitory receptors, pre- and post-stimulation. In contrast, memory CD8⁺ T-cells predominantly expressed TIGIT. The rs763361 TT genotype was associated with both a reduction in CD226 expression on the cell surface of CD4⁺ memory T-cells (P = .004) and increased interleukin-17A secretion from activated T-cells (P = .036). Description of different expression patterns on T lymphocyte subpopulations provided in this work will lead to a more comprehensive understanding of the role of the CD226/TIGIT axis in control over T-cell activation and suppression.

中文翻译：

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人类 CD4+ 和 CD8+ T 淋巴细胞亚群具有显着不同的 CD226 和 TIGIT 分子的表面表达模式

CD226 和抑制性 T 细胞免疫球蛋白和 ITIM 结构域 (TIGIT) 属于在 T 细胞和自然杀伤细胞中发现的共刺激受体系统。尽管来自全基因组研究的数据表明 CD226 基因座与多种自身免疫性疾病之间存在很强的关联，但对人类 T 细胞亚群激活过程中 CD226/TIGIT 轴平衡的理解仍然不完整。在这项研究中，我们旨在比较 CD226 和 TIGIT 与 CD28 在人 CD4 ⁺和 CD8 ^{+中的刺激前和刺激后表达谱}使用流式细胞术的 T 细胞亚群。还检查了 CD226 单核苷酸多态性 rs763361 对细胞表面 CD226 表达和效应细胞因子分泌的影响。研究了来自健康献血者 (n = 65) 的外周血单个核细胞。大多数初始 CD4 ⁺和 CD8 ⁺ T 细胞不表达 CD226 和 TIGIT，主要是在刺激后上调激活受体。记忆 CD4 ⁺ T 细胞在刺激前和刺激后表现出激活和抑制受体的平衡表达。相比之下，记忆 CD8 ⁺ T 细胞主要表达 TIGIT。rs763361 TT 基因型与 CD4 ^{+细胞表面上 CD226 表达的减少有关}记忆 T 细胞 ( P  = .004) 和活化 T 细胞分泌的白细胞介素 17A 增加 ( P  = .036)。在这项工作中提供的对 T 淋巴细胞亚群不同表达模式的描述将有助于更全面地了解 CD226/TIGIT 轴在控制 T 细胞活化和抑制中的作用。