Perturbation of the T-cell repertoire in patients with unstable angina
Perturbation of the T-cell repertoire in patients with unstable angina
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DOI：
10.1161/01.cir.100.21.2135
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发表时间：
1999-11-23
期刊：
影响因子：
37.8
通讯作者：
Weyand, CM
中科院分区：
文献类型：
--
作者：
Liuzzo, G;Kopecky, SL;Weyand, CM
背景：单核细胞在不稳定心绞痛（UA）中被组成性激活，导致IL-6的产生和急性期蛋白的上调。潜在的机制尚不清楚。为了探讨强作用单核细胞激活剂ifn - γ的产生是否在UA中发生改变，我们比较了UA（布劳恩瓦尔德IIIB级）和稳定型心绞痛（SA）患者T淋巴细胞产生的细胞因子。方法与结果：分别于住院时、2周、12周采集外周血淋巴细胞。细胞因子生成CD4（+）和CD8(+) T细胞在三色流式细胞术中定量，用肉豆酸酯和离子霉素刺激后，UA与产生ifn - γ的CD4（+）和CD8+ T细胞数量增加有关，而SA患者的IL-2（+）和IL-4(+) CD4(+) T细胞的频率更高。UA患者ifn - γ (+) t细胞群的扩增持续至少3个月。UA中ifn - γ产生的增加可归因于T细胞中一个不寻常的亚群CD4(+)CD28(null) T细胞的扩增。结论：UA患者的特征是功能性t细胞库的扰动，偏向于ifn - γ的产生，这表明单核细胞激活和急性期反应是t细胞激活的结果。ifn - γ是由CD4(+)CD28(null) T细胞产生的，它在UA中扩增，在SA和对照组中明显低，CD4(+)CD28(null) T细胞的出现可能是由于持续的抗原刺激。
Background-Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA).Methods and Results-Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4(+) and CD8(+) T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin, UA was associated with an increased number of CD4(+) and CD8+ T cells producing IFN-gamma, whereas patients with SA had higher frequencies of IL-2(+) and IL-4(+) CD4(+) T cells. Expansion of the IFN-gamma(+) T-cell population in UA persisted for at least 3 months. Increased production of IFN-gamma in UA could be attributed to the expansion of an unusual subset of T cells, CD4(+)CD28(null) T cells.Conclusions-Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-gamma production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-gamma is produced by CD4(+)CD28(null) T cells, which are expanded in UA and distinctly low in SA and controls, The emergence of CD4(+)CD28(null) T cells may result from persistent antigenic stimulation.