Human CD4⁺ and CD8⁺ T lymphocyte subpopulations have significantly different surface expression patterns of CD226 and...

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.