Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells

Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells
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DOI:
10.1111/j.1365-2133.2009.09573.x
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发表时间:
2010-04-01
影响因子:
10.3
通讯作者:
von Stebut, E.
von Stebut, E.
中科院分区:
医学1区
文献类型:
--
作者:
Geiger, B.;Wenzel, J.;von Stebut, E.

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皮肤利什曼病(CL)是一种流行性疾病,在全世界范围内影响数百万人.治疗方案有几个副作用和疫苗并不存在,目前。ObjectivesTo翻译信息对CL从小鼠到人的保护,我们研究了CL皮肤活检的局部免疫反应,并将这些结果与临床information.MethodsThe炎症细胞的频率确定在皮肤活检的20例患者诊断为CL使用免疫组化。此外,由此产生的适应性免疫反应的性质进行了评估(双重)免疫染色对CD 4和趋化因子受体CXCR 3(辅助性T细胞1,Th 1)/CCR 4(Th 2)。CD 1a+表皮朗格汉斯细胞不存在以上的病变中心,但正常分布在周围组织。肥大细胞和CD 56+自然杀伤细胞数量不受影响。有趣的是,CCR 4 + Th 2细胞在20个样品中均未检测到。相反,浸润的CXCR 3+细胞的数量很高,并且这些细胞中的大多数是CD 4+或CD 8+,表明它们代表产生干扰素-γ的Th 1/T细胞毒性1型(Tc 1)细胞。最后,这些发现与获得感染的国家或患者的年龄或性别的临床信息无关。然而,病变已经持续了6个月以上,含有较少的CXCR 3 + CD 4和CD 8 T细胞比那些已经持续了不到6 months.ConclusionsOur数据对人类CL病变的炎症浸润强调的相关性,在实验模型中获得的结果。Th 1和Tc 1细胞似乎对小鼠和人的CL愈合至关重要。
P>BackgroundCutaneous leishmaniasis (CL) is an epidemic disease affecting millions of individuals worldwide. Treatment options have several side-effects and a vaccine does not exist at present.ObjectivesTo translate information about protection against CL from mice to man, we studied the local immune response in CL skin biopsies and correlated these findings with clinical information.MethodsThe frequency of inflammatory cells was determined in skin biopsies of 20 patients diagnosed with CL using immunohistochemistry. In addition, the nature of the resulting adaptive immune response was assessed by (double) immunostaining against CD4 and chemokine receptors CXCR3 (T helper 1, Th1)/CCR4 (Th2).ResultsAll lesions contained CD4+ and CD8+ T cells, B cells and CD68+ macrophages. CD1a+ epidermal Langerhans cells were absent above the centre of the lesions, but normally distributed in the surrounding tissue. Mast cell and CD56+ natural killer cell numbers were not affected. Interestingly, CCR4+ Th2 cells were not detected in any of the 20 samples. In contrast, the number of infiltrating CXCR3+ cells was high and the majority of these were CD4+ or CD8+ indicating that they represent interferon-gamma-producing Th1/T cytotoxic type 1 (Tc1) cells. Finally, these findings did not correlate with clinical information about the country where the infection was acquired, or age or sex of the patients. However, lesions that had already persisted for more than 6 months contained fewer CXCR3+ CD4 and CD8 T cells than those that had persisted for less than 6 months.ConclusionsOur data on the inflammatory infiltrate of human CL lesions underline the relevance of findings obtained in experimental models. Both Th1 and Tc1 cells appear to be critical for healing in CL in mouse and man.