Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis
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DOI:
10.1128/cvi.00390-12
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发表时间:
2012-10-01
影响因子:
--
通讯作者:
Garcia, Luis F.
Garcia, Luis F.
中科院分区:
生物3区
文献类型:
--
作者:
Marin, Nancy D.;Paris, Sara C.;Garcia, Luis F.

文献摘要

被引文献

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活动性结核病患者结核分枝杆菌T细胞亚群的表型和功能改变已有报道。更好地了解这些变化将增加有关免疫发病机制的知识,也可能有助于开发新的诊断和预防策略。在此,我们研究了CD 4(+)和CD 8(+)T细胞的体外表型以及γ干扰素的频率和表型。在未感染者(非TBi)、潜伏感染者(LTBi)、活动性肺结核(ATB)患者。T细胞的表型表征基于⑶ 45 R 0和⑶ 27的表达进行。结果表明,ATB降低了循环CD 4(+)CD 45 RO(+)CD 27(+)T细胞的频率,增加了CD 4(+)CD 45 RO(-)CD 27(+)T细胞的频率。PPD刺激后,ATB的循环中产生IL-17的CD 4(+)T细胞的频率也高于LTBi,而LTBi的产生IFN-γ的CD 4(+)T细胞的频率高于非TBi。24 h时IFN-γ产生细胞的表型与IL-17产生细胞的表型不同,LTBi和ATB之间无差异。在144 h时,IFN-γ和IFN-γ IL-17产生细胞主要是CD 45 RO(+)CD 27(+)T细胞,并且在ATB中更常见。这些结果表明M.结核感染诱导T细胞的改变,其干扰足够的特异性免疫应答。
Phenotypic and functional alterations in Mycobacterium tuberculosis T cell subsets have been reported in patients with active tuberculosis. A better understanding of these alterations will increase the knowledge about immunopathogenesis and also may contribute to the development of new diagnostics and prophylactic strategies. Here, the ex vivo phenotype of CD4(+) and CD8(+) T cells and the frequency and phenotype of gamma interferon (IFN-gamma)- and interleukin 17 (IL-17)-producing cells elicited in shortterm and long-term cultures following CFP-10 and purified protein derivative (PPD) stimulation were determined in noninfected persons (non-TBi), latently infected persons (LTBi), and patients with active tuberculosis (ATB). Phenotypic characterization of T cells was done based on the expression of CD45RO and CD27. Results show that ATB had a reduced frequency of circulating CD4(+) CD45RO(+) CD27(+) T cells and an increased frequency of CD4(+) CD45RO(-) CD27(+) T cells. ATB also had a higher frequency of circulating IL-17-producing CD4(+) T cells than did LTBi after PPD stimulation, whereas LTBi had more IFN-gamma-producing CD4(+) T cells than did non-TBi. The phenotype of IFN-gamma -producing cells at 24 h differs from the phenotype of IL-17-producing cells with no differences between LTBi and ATB. At 144 h, IFN-gamma- and IFN-gamma IL-17-producing cells were mainly CD45RO(+) CD27(+) T cells and they were more frequent in ATB. These results suggest that M. tuberculosis infection induces alterations in T cells which interfere with an adequate specific immune response.