Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
Am J Trop Med Hyg. 2012 May;86(5):878-83. doi: 10.4269/ajtmh.2012.12-0088.
T regulatory cells (Tregs) play an important role in the mechanism of host's failure to control pathogen dissemination in severe forms of different chronic granulomatous diseases, but their role in leprosy has not yet been elucidated; 28 newly diagnosed patients (16 patients with lepromatous leprosy and 12 patients with tuberculoid leprosy) and 6 healthy Mycobacterium leprae-exposed individuals (contacts) were studied. Tregs were quantified by flow cytometry (CD4+ CD25+ Foxp3+) in peripheral blood mononuclear cells stimulated in vitro with a M. leprae antigenic preparation and phytohemagglutinin as well as in skin lesions by immunohistochemistry. The lymphoproliferative (LPR), interleukin-10 (IL-10), and interferon-γ (IFN-γ) responses of the in vitro-stimulated peripheral blood mononuclear cells and the in situ expression of IL-10, transforming growth factor-β (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were also determined. We show that M. leprae antigens induced significantly lower LPR but significantly higher Treg numbers in lepromatous than tuberculoid patients and contacts. Mitogen-induced LPR and Treg frequencies were not significantly different among the three groups. Tregs were also more frequent in situ in lepromatous patients, and this finding was paralleled by increased expression of the antiinflammatory molecules IL-10 and CTLA-4 but not TGF-β. In lepromatous patients, Tregs were intermingled with vacuolized hystiocyte infiltrates all over the lesion, whereas in tuberculoid patients, Tregs were rare. Our results suggest that Tregs are present in increased numbers, and they may have a pathogenic role in leprosy patients harboring uncontrolled bacillary multiplication but not in those individuals capable of limiting M. leprae growth.
调节性 T 细胞（Tregs）在不同慢性肉芽肿性疾病的严重形式中宿主未能控制病原体传播的机制中发挥重要作用，但它们在麻风病中的作用尚未阐明；研究了 28 例新诊断的患者（16 例麻风瘤型麻风患者和 12 例结核样型麻风患者）和 6 例健康的麻风分枝杆菌暴露个体（接触者）。通过流式细胞术（CD4+CD25+Foxp3+）在外周血单个核细胞中定量检测 Tregs，这些细胞在体外用麻风分枝杆菌抗原制剂和植物血凝素刺激，并通过免疫组织化学在皮肤病变中检测。还测定了体外刺激的外周血单个核细胞的淋巴增殖（LPR）、白细胞介素 10（IL-10）和干扰素-γ（IFN-γ）反应以及原位表达的白细胞介素 10、转化生长因子-β（TGF-β）和细胞毒性 T 淋巴细胞抗原 4（CTLA-4）。结果表明，麻风分枝杆菌抗原诱导的 LPR 显著低于瘤型患者和接触者，但 Treg 数量显著高于瘤型患者和接触者。有丝分裂原诱导的 LPR 和 Treg 频率在三组之间无显著差异。Tregs 在瘤型患者中也更为常见，这一发现与抗炎分子白细胞介素 10 和 CTLA-4 的表达增加平行，但 TGF-β的表达没有增加。在瘤型患者中，Tregs 与遍布病变的空泡化组织细胞浸润物交织在一起，而在结核样型患者中，Tregs 很少见。我们的结果表明，Tregs 数量增加，它们可能在携带未受控制的细菌繁殖的麻风病患者中具有致病性作用，但在能够限制麻风分枝杆菌生长的个体中则没有。
