T-cell regulation in lepromatous leprosy.
T-cell regulation in lepromatous leprosy.
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DOI：
10.1371/journal.pntd.0002773
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Geluk A
中科院分区：
文献类型：
--
作者：
Bobosha K;Wilson L;van Meijgaarden KE;Bekele Y;Zewdie M;van der Ploeg-van Schip JJ;Abebe M;Hussein J;Khadge S;Neupane KD;Hagge DA;Jordanova ES;Aseffa A;Ottenhoff TH;Geluk A
调节性T（Treg）细胞因其在自身免疫性疾病和慢性感染中维持自身耐受和平衡免疫反应的作用而闻名。然而，调节机制也可能导致麻风病和结核病等慢性感染中病原体的存活时间延长。尽管对麻风分枝杆菌（M.麻风（Leprae），瘤型麻风（LL）患者具有不能产生针对细菌的辅助性T细胞1（Th 1）应答的特征。在这项研究中，我们调查了对M。通过分析IFN-γ对M.通过PBMC细胞亚群分析和患者皮损的免疫组化，对CD 25+细胞去除前后的麻风进行了研究。总PBMC中CD 25+细胞的耗竭鉴定了两组LL患者：7/18（38.8%）获得了对M的体外应答性。CD 25+细胞耗竭后，麻风细胞逆转为M。通过添加自体CD 25+细胞的麻风特异性T细胞无反应性。相反，11/18（61.1%）在缺乏CD 25 + T细胞的情况下仍然无反应性。然而，对于两组，有丝分裂原诱导的IFN-γ不受CD 25+细胞耗竭的影响。In M.在麻风应答的健康对照、治疗的瘤型麻风（LL）和边缘型结核样麻风（BT）患者中，CD 25+细胞的耗竭仅轻微增加IFN-γ应答。此外，细胞亚群分析显示，与BT患者相比，LL中FoxP 3 + CD 8 + CD 25 + T细胞的数量显著更高（p=0.02），而皮肤活检的共聚焦显微镜显示，与结核样和交界性结核样麻风（TT/BT）病变相比，LL病变中CD 68 + CD 163+和FoxP 3+细胞的数量增加。 因此，这些数据表明，CD 25 + Treg细胞在M. LL中的麻风-Th 1无反应性。麻风病是由麻风分枝杆菌（M. leprae）引起的一种可治愈的传染病。麻风病）影响皮肤和周围神经。它表现为不同的形式，从自愈，结核样麻风（TT）与低菌负荷和高细胞免疫对M。从麻风病人到瘤型麻风（LL），具有高菌载量和高抗体滴度。麻风抗原然而，LL患者对M的细胞介导应答较差。导致细菌清除延迟的麻风病。这种细菌持久性的一个可能解释可能在于感染部位和外周血中存在更多的调节细胞。该研究显示，通过在LL患者亚组中耗尽CD 25+细胞，细胞介导的应答恢复，而另一患者亚组未受到类似影响。此外，在LL患者的皮肤活检中观察到FoxP 3 + T细胞与抗炎巨噬细胞的频率增加。因此，这些数据表明，CD 25 + Treg细胞在M.麻风病人的麻风无反应性。
Regulatory T (Treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25+ cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients' skin lesions. Depletion of CD25+ cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25+ cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25+ cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25+ T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25+ cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25+ cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3+ CD8+CD25+ T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68+CD163+ as well as FoxP3+ cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25+ Treg cells play a role in M. leprae-Th1 unresponsiveness in LL. Leprosy is a curable infectious disease caused by Mycobacterium leprae (M. leprae) that affects the skin and peripheral nerves. It is manifested in different forms ranging from self-healing, tuberculoid leprosy (TT) with low bacillary load and high cellular immunity against M. leprae, to lepromatous leprosy (LL) with high bacillary load and high antibody titers to M. leprae antigens. However, LL patients have poor cell mediated response against M. leprae leading to delayed clearance of the bacilli. A possible explanation for this bacterial persistence could lie in the presence of more regulatory cells at infection sites and in peripheral blood. This study shows the recovery of the cell mediated response by depletion of CD25+ cells in a subset of LL patients, while another patient subset was not affected similarly. Moreover, an increased frequency of FoxP3+ T cells together with anti-inflammatory macrophages was observed in LL patients' skin biopsies. Thus, these data show that CD25+ Treg cells play a role in M. leprae-unresponsiveness in leprosy patients.
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影响因子：
9.1
作者：
Geluk, Annemieke;van Meijgaarden, Krista E.;Ottenhoff, Tom H. M.
通讯作者：
Ottenhoff, Tom H. M.
影响因子：
3.6
作者：
Attia, Enas A. S.;Abdallah, Marwa;Ali, Hala B.
通讯作者：
Ali, Hala B.
DOI：
10.4049/jimmunol.0803474
发表时间：
2010-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Moncrieffe H;Nistala K;Kamhieh Y;Evans J;Eddaoudi A;Eaton S;Wedderburn LR
通讯作者：
Wedderburn LR
影响因子：
5.4
作者：
Boer, Mardi C.;van Meijgaarden, Krista E.;Joosten, Simone A.
通讯作者：
Joosten, Simone A.
DOI：
10.1073/pnas.0702257104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Joosten, Simone A.;van Meijgaarden, Krista E.;Ottenhoff, Tom H. M.
通讯作者：
Ottenhoff, Tom H. M.