de Boer O J, van der Wal A C, Houtkamp M A, Ossewaarde J M, Teeling P, Becker A E
Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Cardiovasc Res. 2000 Dec;48(3):402-8. doi: 10.1016/s0008-6363(00)00195-4.
Atherosclerotic lesions are characterized by an immune mediated chronic inflammation. Seroepidemiological studies support a relationship between atherosclerotic disease and infection with C. pneumoniae; an association further endorsed by immunocytochemical and DNA directed studies. However, the question arises whether C. pneumoniae acts as a causal antigen, or is merely a bystander. For this reason we have analyzed the T lymphocyte population of carotid atherosclerotic plaques of symptomatic patients for their response against C. pneumoniae.
T cell lines were generated from carotid endarterectomy tissues obtained from eight patients with symptomatic disease. The response of these T cell lines against C. pneumoniae elementary bodies was analyzed by 3H-thymidine incorporation. T cell clones were generated by limiting dilution from the cell lines of three patients and tested for antigen specificity in the same manner. Furthermore, cytokine profiles (Th1/Th0/Th2) were established by measuring the production of IFN-gamma and IL-4.
Of the eight T-cell lines five responded to C. pneumoniae. Eighteen of 69 CD4-positive clones, generated from three patients with a positive T cell lines response, responded to C. pneumoniae also. The majority (17/18, 96%) of these clones showed a Th1 cytokine profile.
These results show that in a subpopulation of symptomatic patients C. pneumoniae can activate T cells within atherosclerotic plaques suggesting that a C. pneumoniae enhanced proinflammatory Th1 response contributes to plaque destabilization in these patients.
动脉粥样硬化病变的特征是免疫介导的慢性炎症。血清流行病学研究支持动脉粥样硬化疾病与肺炎衣原体感染之间存在关联；免疫细胞化学和DNA定向研究进一步证实了这种关联。然而，问题在于肺炎衣原体是作为致病抗原，还是仅仅是一个旁观者。因此，我们分析了有症状患者颈动脉粥样硬化斑块中的T淋巴细胞群体对肺炎衣原体的反应。
从8例有症状疾病患者的颈动脉内膜切除术组织中生成T细胞系。通过3H-胸腺嘧啶核苷掺入分析这些T细胞系对肺炎衣原体原体的反应。通过有限稀释从3例患者的细胞系中生成T细胞克隆，并以相同方式测试其抗原特异性。此外，通过测量IFN-γ和IL-4的产生来确定细胞因子谱（Th1/Th0/Th2）。
8个T细胞系中有5个对肺炎衣原体有反应。从3例T细胞系反应阳性的患者中产生的69个CD4阳性克隆中有18个也对肺炎衣原体有反应。这些克隆中的大多数（17/18，96%）显示出Th1细胞因子谱。
这些结果表明，在一部分有症状的患者中，肺炎衣原体可激活动脉粥样硬化斑块内的T细胞，提示肺炎衣原体增强的促炎性Th1反应导致这些患者的斑块不稳定。
