Activating NK-cell receptors co-stimulate CD4+CD28- T cells in patients with rheumatoid arthritis
Activating NK-cell receptors co-stimulate CD4+CD28- T cells in patients with rheumatoid arthritis
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DOI：
10.1002/eji.200939399
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Malmstrom, Vivianne
中科院分区：
文献类型：
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作者：
Fasth, Andreas E. R.;Bjorkstrom, Niklas K.;Malmstrom, Vivianne
效应T细胞应答可以通过竞争NK细胞受体（NKR）转导的阳性或阴性信号来调节。在CD 4（+）T细胞群中，NKR的表达主要见于CD 4（+）CD 28（-）T细胞亚群，也称为CD 28（空）T细胞。这些T细胞经常在类风湿性关节炎（RA）和其他炎症性疾病中发现，表明通过NKR的信号传导可能在自身免疫反应中发挥作用。本研究旨在探讨RA患者表达NKR的CD 4（+）CD 28（-）T细胞的表型和功能。通过分析CD 4（+）CD 28（-）T细胞上的大量NKR，我们发现共活化受体2B 4（CD 244）、DNAM-1（CD 226）和CRACC的显著表达。2B 4与DNAM-1和/或NKG 2D的成对连接导致原代CD 4（+）CD 28（-）T细胞的效应子功能增加至抗CD 3刺激的次优水平。使用多参数流式细胞术，我们证明，这种coligation导致整体反应性的幅度增加，而不改变反应的定性方面。总之，这些结果证明了RA中NKR介导的CD 4（+）CD 28（-）T细胞功能调节的累加效应模式。这可能会对这些细胞施加的炎症反应产生影响，从而影响疾病的表现。
Effector T-cell responses can be modulated by competing positive or negative signals transduced by NK-cell receptors (NKR). In the CD4(+) T-cell population, the expression of NKR is primarily found in the CD4(+)CD28(-) T-cell subset, also known as CD28(null) T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR-expressing CD4(+) CD28(-) T cells in patients with RA. By analyzing a broad array of NKR on CD4(+)CD28(-) T cells we found a significant expression of the co-activating receptors 2B4 (CD244), DNAM-1 (CD226), and CRACC. Pair-wise ligations of 2B4 with DNAM-1 and/or NKG2D lead to increased effector functions of primary CD4(+)CD28(-) T cells to suboptimal levels of anti-CD3 stimulation. Using multi-parameter flow cytometry, we demonstrate that such coligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR-mediated functional modulation of CD4(+)CD28(-) T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.