CD4+CD28null T cells in autoimmune disease:: Pathogenic features and decreased susceptibility to immunoregulation
CD4+CD28null T cells in autoimmune disease:: Pathogenic features and decreased susceptibility to immunoregulation
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DOI：
10.4049/jimmunol.179.10.6514
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Stinissen, Piet
中科院分区：
文献类型：
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作者：
Thewissen, Marielle;Somers, Veerle;Stinissen, Piet
为了确定扩增的CD4(+)CD28(空)T细胞在多发性硬化症和类风湿关节炎病理中的作用，对这些细胞进行了表型鉴定和抗原反应性研究。流式细胞仪分析证实，CD4(+)CD28(空)T细胞是终末分化的效应记忆细胞。此外，它们还表达表型标志物，表明它们有能力渗透到组织中并造成组织损伤。虽然在CD4(+)CD28(空)T细胞亚群中没有观察到对候选自身抗原髓鞘碱性蛋白和11型胶原的反应，但在4例HC、4例类风湿性关节炎患者和3例多发性硬化症患者中，CMV反应显著。研究发现，CMV诱导的增殖反应水平与反应的克隆多样性有关。有趣的是，我们的结果表明，CD4(+)CD28(空)T细胞对CD4(+)CD25(+)调节性T细胞的抑制作用不敏感。总之，这项研究为CD4(+)CD28(空)T细胞在自身免疫病理中的作用提供了几个适应症。CD4(+)CD28(空)T细胞表现出致病特性，填充免疫空间，对调节机制不太敏感。然而，基于它们对本研究中测试的自身抗原的低反应性，CD4(+)CD28(空)T细胞很可能在自身免疫性疾病中不起直接的自身侵袭性作用。
To determine the role of expanded CD4(+)CD28(null) T cells in multiple sclerosis and rheumatoid arthritis pathology, these cells were phenotypically characterized and their Ag reactivity was studied. FACS analysis confirmed that CD4(+)CD28(null) T cells are terminally differentiated effector memory cells. In addition, they express phenotypic markers that indicate their capacity to infiltrate into tissues and cause tissue damage. Whereas no reactivity to the candidate autoantigens myelin basic protein and collagen type 11 was observed within the CD4(+)CD28(null) T cell subset, CMV reactivity was prominent in four of four HC, four of four rheumatoid arthritis patients, and three of four multiple sclerosis patients. The level of the CMV-induced proliferative response was found to be related to the clonal diversity of the response. Interestingly, our results illustrate that CD4(+)CD28(null) T cells are not susceptible to the suppressive actions of CD4(+)CD25(+) regulatory T cells. In conclusion, this study provides several indications for a role of CD4(+)CD28(null) T cells in autoimmune pathology. CD4(+)CD28(null) T cells display pathogenic features, fill up immunological space, and are less susceptible to regulatory mechanisms. However, based on their low reactivity to the autoantigens tested in this study, CD4(+)CD28(null) T cells most likely do not play a direct autoaggressive role in autoimmune disease.