Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis Due to Leishmania guyanensis
Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis Due to Leishmania guyanensis
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DOI：
10.1128/iai.01398-08
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发表时间：
2009-04-01
影响因子：
3.1
通讯作者：
Launois, P.
中科院分区：
文献类型：
--
作者：
Bourreau, E.;Ronet, C.;Launois, P.
通过Foxp3基因表达分析，检测了急性皮肤利什曼病(ACL)和慢性皮肤利什曼病(CCL)患者皮损中调节性T细胞(Treg细胞)的水平。我们证明，在感染的早期阶段(病变持续时间不到1个月)，Treg细胞优先在前交叉韧带患者的皮损中聚集。此外，CCL患者的Foxp3mRNA转录本水平显著高于ACL患者，提示病变内Treg细胞在CCL中起着关键作用。来自ACL和CCL患者的病变内Treg细胞在体外被证明具有抑制功能，因为它们抑制从同一患者外周血单个核细胞中提纯的CD4(+)CD25(-)T细胞产生的干扰素(干扰素-γ)，以响应古扬利什曼原虫的刺激。瘤内2，3-吲哚-胺双加氧酶(IDO)的表达与Foxp3的表达相关，提示IDO在抑制瘤内Treg细胞的活性中起作用。此外，白介素10(IL-10)的作用虽然很小，但也得到了证实，因为在体外抑制试验中，病变内T细胞产生的IL-10的中和增加了效应细胞产生的干扰素-γ。这些结果证实了病变内Treg细胞在人类利什曼原虫感染的免疫发病机制中的作用，特别是在CCL患者中。
The levels of regulatory T cells (Treg cells), analyzed by Foxp3 mRNA expression, were determined in lesions from patients with acute cutaneous leishmaniasis (ACL) and chronic cutaneous leishmaniasis (CCL). We demonstrated that Treg cells preferentially accumulate in lesions from ACL patients during the early phase of infection (lesion duration of less than 1 month). In addition, levels of Foxp3 mRNA transcripts were significantly higher in specimens from patients with CCL than in those from patients with ACL, suggesting a critical role of intralesional Treg cells in CCL. Intralesional Treg cells from both ACL and CCL patients were shown to have suppressive functions in vitro, since they inhibited the gamma interferon (IFN-gamma) produced by CD4(+) CD25(-) T cells purified from peripheral blood mononuclear cells from the same patient in response to Leishmania guyanensis stimulation. Intralesional 2,3-indoleamine dioxygenase (IDO) mRNA expression was associated with that of Foxp3, suggesting a role for IDO in the suppressive activity of intralesional Treg cells. In addition, a role, albeit minor, of interleukin-10 (IL-10) was also demonstrated, since neutralization of IL-10 produced by intralesional T cells increased IFN-gamma production by effector cells in an in vitro suppressive assay. These results confirm the role of intralesional Treg cells in the immunopathogenesis of human Leishmania infection, particularly in CCL patients.