Expansion of unusual CD4+ T cells in severe rheumatoid arthritis
Expansion of unusual CD4+ T cells in severe rheumatoid arthritis
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DOI：
10.1002/art.1780400615
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发表时间：
1997-06-01
影响因子：
--
通讯作者：
Weyand, CM
中科院分区：
文献类型：
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作者：
Martens, PB;Goronzy, JJ;Weyand, CM
目标。类风湿性关节炎(RA)患者的T细胞以克隆性增殖为特征，这些细胞是自身反应性的，缺乏重要的功能分子CD28的表达，本研究的目的是确定这些异常淋巴细胞在疾病过程中的作用。采用双色荧光活化细胞分析仪检测108例RA患者和53例正常人外周血中CD4+CD28-T细胞的表达，并对临床资料进行回顾性分析。CD_4+CD_(28)-T细胞的频率呈双峰分布，区分了正常人和RA患者中的携带者和非携带者。纵向研究中，非携带者和非携带者的表型随时间的推移而稳定，CD_4+CD_(28-)T细胞的携带者在RA人群中累积(%对45%；P=0.02)，CD_4+CD_(28-T)细胞的增多与关节外受累有关，而与病程、抗风湿治疗或关节破坏的严重程度无关，以结节性疾病(P=0.02)和类风湿器官疾病(P=0.04)患者亚群中CD_4+CD_(28-T)细胞携带者比例最高。CD_4+CD_(28)细胞的大小与RA关节外进展有关(结节性RA P=0.001，类风湿器官疾病P=0.003)。CD4+CD28-T细胞频率分布的双峰性与这些异常T细胞的产生的遗传控制相一致，在RA患者中，CD4+CD28-T细胞不是疾病过程中的一种偶然现象，而是使患者容易发生关节外组织的炎性病变。
Objective. The repertoire of T cells in patients with rheumatoid arthritis (RA) is characterized by clonal expansion of selected CD4+ T cells, which are autoreactive and lack the expression of the functionally important CD28 molecule, The goal of this study was to determine the contribution of these unusual lymphocytes to the disease process.Methods. RA patients (n = 108) and normal controls (n = 53) were examined for the expression of CD4+CD28- T cells by 2-color fluorescence-activated cell sorter analysis, Clinical data were ascertained by retrospective chart review.Results. The frequencies of CD4+CD28- T cells displayed a bimodal distribution, defining carriers and noncarriers in normal subjects and RA patients, In longitudinal studies, the noncarrier and carrier phenotypes were stable over time, Carriers of CD4+CD28- T cells accumulated in the RA population (64% versus 45%; P = 0.02), The expansion of CD4+CD28- T cells correlated with extraarticular involvement, but not with disease duration, antirheumatic treatment, or severity of joint destruction, The patient subsets with nodular disease (P = 0.02) and rheumatoid organ disease (P = 0.04) had the highest proportion of CD4+CD28- T cell carriers. The size of the CD4+CD28- compartment correlated with extraarticular progression of RA (P = 0.001 in nodular RA, P = 0.003 in rheumatoid organ disease).Conclusion. The bimodality of distribution of CD4+CD28- T cell frequencies is compatible with genetic control of the generation of these unusual T cells, In RA patients, CD4+CD28- T cells are not an epiphenomenon of the disease process, but predispose patients to developing inflammatory lesions in extraarticular tissues.