IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus
IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus
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DOI：
10.1093/rheumatology/kes100
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发表时间：
2012-09-01
期刊：
影响因子：
5.5
通讯作者：
Kim, Hang-Rae
中科院分区：
文献类型：
--
作者：
Kim, Jung-Sik;Cho, Bon-A;Kim, Hang-Rae
目标。人效应记忆（EM） CD8(+) T细胞包括IL-7R α（高）和IL-7R α（低）细胞，它们具有不同的细胞特征，包括细胞毒性分子的表达。NK细胞和在CD8(+) T细胞上表达的NK细胞相关分子2B4都促进细胞毒性。本研究分析了2B4在IL-7R α（高）和IL-7R α（低）EM CD8(+) T细胞上的表达及其对细胞毒性的贡献。我们还分析了IL-7R α（高）和IL-7R α（低）EM CD8(+) T细胞在SLE或狼疮患者和健康个体中的频率，考虑到细胞毒性CD8(+) T细胞在狼疮发病机制中的潜在作用。我们使用流式细胞术测量了2B4在IL-7R α（高）和IL-7R α（低）EM CD8(+) T细胞上的表达，以及这些细胞群在健康个体和SLE患者外周血中的频率。此外，利用CD48抗原靶细胞，定量研究了2b4介导的IL-7R α（高）和IL-7R α（低）EM CD8(+) T细胞的细胞毒性。我们发现，与IL-7R α（低）EM CD8(+) T细胞相比，IL-7R α（高）EM CD8(+) T细胞具有更高水平的2B4表达。触发2B4可增强IL-7R α（低）EM CD8(+) T细胞对靶细胞的细胞毒功能。我们还注意到SLE患者IL-7R α（低）EM CD8(+) T细胞频率增加，这与疾病表现相关。我们的研究结果表明SLE患者IL-7R α（低）EM CD8(+) T细胞增加，可能通过2b4介导的细胞毒性导致组织损伤。
Objective. Human effector memory (EM) CD8(+) T cells include IL-7R alpha(high) and IL-7R alpha(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus.Methods. We used flow cytometry to measure the expression of 2B4 on IL-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7R alpha(high) and IL-7R alpha(low) EM CD8(+) T cells using target cells with CD48 antigen.Results. We found that IL-7R alpha(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7R alpha(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7R alpha(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7R alpha(low) EM CD8(+) T cells that correlated with disease manifestation.Conclusion. Our findings show that SLE patients have increased IL-7R alpha(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.