In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans
In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans
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DOI：
10.1016/j.micinf.2007.06.004
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Mascart, Francoise
中科院分区：
文献类型：
--
作者：
Hougardy, Jean-Michel;Verscheure, Virginie;Mascart, Francoise
与结核分枝杆菌潜伏感染（LTB1）健康个体和未感染对照相比，最近发现结核患者外周血中CD4(+)CD25（高）FOXP3（+）调节性T （Treg）细胞水平升高。在这里，我们发现CD4(+)CD25（高）FOXP3(+) T淋巴细胞可以在体外从LTBI个体的外周血单个核细胞（PBMC）中扩增，但在tgf - β存在的情况下，通过与卡介苗一起培养，未感染的对照组不能扩增。这些来自LTBI受试者PBMC的扩增细胞表达CTLA-4、GITR和OX-40，但CD127（低/-），因此具有Treg细胞的表型。此外，它们以剂量依赖的方式抑制新分离的单核细胞对多克隆刺激的增殖，表明它们是功能性Treg淋巴细胞。相比之下，PBMC与BCG单独孵育优先诱导活化的CD4(+) T细胞，表达CD25和/或CD69并分泌ifn - γ。这些结果表明，CD4(+)CD25（高）FOXP3(+) Treg细胞可以在LTBI患者的外周血中扩增或诱导，这些患者已知易患活动性结核病，因此可能在该病的发病机制中发挥重要作用。(C) 2007 Elsevier Masson SAS。版权所有。
CD4(+)CD25(high)FOXP3(+) regulatory T (Treg) cells have recently been found at elevated levels in the peripheral blood of tuberculosis patients, compared to Mycobacterium tuberculosis latently infected (LTB1) healthy individuals and non-infected controls. Here, we show that CD4(+)CD25(high)FOXP3(+) T lymphocytes can be expanded in vitro from peripheral blood mononuclear cells (PBMC) of LTBI individuals, but not of uninfected controls by incubating them with BCG in the presence of TGF-beta. These expanded cells from the PBMC of LTBI subjects expressed CTLA-4, GITR and OX-40, but were CD127(low/-) and have therefore the phenotype of Treg cells. In addition, they inhibited in a dose-dependant manner the proliferation of freshly isolated mononuclear cells in response to polyclonal stimulation, indicating that they are functional Treg lymphocytes. In contrast, incubation of the PBMC with BCG alone preferentially induced activated CD4(+) T cells, expressing CD25 and/or CD69 and secreting IFN-gamma. These results show that CD4(+)CD25(high)FOXP3(+) Treg cells can be expanded or induced in the peripheral blood of LTBI individuals in conditions known to predispose to progression towards active tuberculosis and may therefore play an important role in the pathogenesis of the disease. (C) 2007 Elsevier Masson SAS. All rights reserved.