CD28nullCD4+ T cells -: Characterization of an effector memory T-cell population in patients with rheumatoid arthritis
CD28nullCD4+ T cells -: Characterization of an effector memory T-cell population in patients with rheumatoid arthritis
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DOI：
10.1111/j.0300-9475.2004.01464.x
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发表时间：
2004-08-01
影响因子：
3.7
通讯作者：
Malmström, V
中科院分区：
文献类型：
--
作者：
Fasth, AER;Cao, D;Malmström, V
缺乏共刺激分子CD 28的CD 4（+）T细胞在老年人和慢性炎症性疾病中均有描述，其中之一是类风湿性关节炎（RA）。在这项研究中，我们提供了一个全面的表征细胞表面标志物和功能的CD 28（空）CD 4（+）T细胞，以及与临床参数的相关性。我们的结论是，与这些细胞相关的所有表面标志物中，只有CD 57和CD 11b在大多数细胞上表达。该CD 28（null）人群发生在三分之一的RA患者中，与临床特征无关。该群体在外周血中持续存在并扩大，但在大多数患者中被排除在关节之外。在功能上，CD 28（null）CD 4（+）T细胞是有效的效应记忆细胞，就其增殖和细胞毒蛋白分泌特征而言。这种能力与迄今未发表的表面表型相关，细胞均为CCR 7（-）和CD 43（高）。此外，鉴定了新的终末分化的CD 4（+）T细胞的CD 45 RA（+）CCR 7（-）群体。我们认为，在自身免疫性疾病和慢性感染患者的不平衡免疫系统中，能够分泌高水平细胞因子的扩增的CD 28（空）CD 4（+）T细胞群可能有助于疾病表现。
CD4(+) T cells lacking the costimulatory molecule CD28 have been described both in elderly individuals and in chronic inflammatory disorders, one being rheumatoid arthritis (RA). We, in this study, provide a comprehensive characterization of cell surface markers on and function of such CD28(null)CD4(+) T cells, as well as correlations with clinical parameters. We conclude that of all surface markers associated with these cells, only CD57 and CD11b are expressed on the majority of them. This CD28(null) population occurred in one-third of patients with RA and was independent of clinical characteristics. The population was persistent and expanded in peripheral blood, but was excluded from the joint in most patients. Functionally, CD28(null)CD4(+) T cells were potent effector memory cells with regard to their proliferation and cytokine-secretion profiles. This capacity correlated with a hitherto unpublished surface phenotype, the cells being uniformly CCR7(-) and CD43(high). Moreover, a new terminally differentiated CD45RA(+)CCR7(-) population of CD4(+) T cells was identified. We would like to suggest that in the unbalanced immune system of patients with autoimmune disease and chronic infection an expanded CD28(null)CD4(+) T-cell population able to secrete high levels of cytokines is likely to contribute to disease manifestations.