Zal Behnam, Kaski Juan Carlos, Arno Gavin, Akiyu Julius P, Xu Qingbo, Cole Della, Whelan Michael, Russell Nick, Madrigal J Alejandro, Dodi I Anthony, Baboonian Christina
Cardiological Sciences, St George's Hospital Medical School, London, UK.
Circulation. 2004 Mar 16;109(10):1230-5. doi: 10.1161/01.CIR.0000118476.29352.2A. Epub 2004 Mar 1.
CD4+CD28null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome (ACS) compared with patients with chronic stable angina (CSA). The triggers of activation and expansion of these cells to date remain unclear.
Twenty-one patients with ACS and 12 CSA patients with angiographically confirmed coronary artery disease and 9 healthy volunteers were investigated. Peripheral blood leukocytes were stimulated with human cytomegalovirus (HCMV), Chlamydia pneumoniae, human heat-shock protein 60 (hHSP60), or oxidized LDL (ox-LDL). CD4+CD28null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-gamma and perforin mRNA transcription as criteria for activation. CD4+CD28null cells from 12 of 21 patients with ACS reacted with hHSP60. No response was detected to HCMV, C pneumoniae, or ox-LDL. Incubation of the cells with anti-MHC class II and anti-CD4 antibodies but not anti-class I antibodies blocked antigen presentation, confirming recognition of the hHSP60 to be via the MHC class II pathway. Patients with CSA had low numbers of CD4+CD28null cells. These cells were nonreactive to any of the antigens used. Circulating CD4+CD28null cells were present in 5 of the 9 healthy controls. None reacted with hHSP60.
We have shown that hHSP60 is an antigen recognized by CD4+CD28null T cells of ACS patients. Endothelial cells express hHSP60 either constitutively or under stress conditions. Circulating hHSP60-specific CD4+CD28null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients.
与慢性稳定型心绞痛（CSA）患者相比，急性冠状动脉综合征（ACS）患者外周血中CD4+CD28阴性T细胞数量增加。迄今为止，这些细胞激活和扩增的触发因素仍不清楚。
对21例ACS患者、12例经血管造影证实患有冠状动脉疾病的CSA患者和9名健康志愿者进行了研究。用人巨细胞病毒（HCMV）、肺炎衣原体、人热休克蛋白60（hHSP60）或氧化型低密度脂蛋白（ox-LDL）刺激外周血白细胞。通过流式细胞术分离CD4+CD28阴性细胞，并以上调干扰素-γ和穿孔素mRNA转录作为激活标准来评估抗原识别情况。21例ACS患者中有12例的CD4+CD28阴性细胞与hHSP60发生反应。未检测到对HCMV、肺炎衣原体或ox-LDL的反应。用抗MHC II类和抗CD4抗体而非抗I类抗体孵育细胞可阻断抗原呈递，证实对hHSP60的识别是通过MHC II类途径。CSA患者的CD4+CD28阴性细胞数量较少。这些细胞对所用的任何抗原均无反应。9名健康对照中有5名存在循环CD4+CD28阴性细胞。无一例与hHSP60发生反应。
我们已表明hHSP60是ACS患者CD4+CD28阴性T细胞识别的一种抗原。内皮细胞在基础状态或应激条件下均表达hHSP60。循环中hHSP60特异性CD4+CD28阴性细胞可能与其他炎症机制一起，导致这些患者的血管损伤。
