Protective and Pathological Functions of CD8+ T Cells in Leishmania braziliensis Infection
Protective and Pathological Functions of CD8+ T Cells in Leishmania braziliensis Infection
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DOI：
10.1128/iai.02404-14
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发表时间：
2015-03-01
影响因子：
3.1
通讯作者：
Bacellar, Olivia
中科院分区：
文献类型：
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作者：
Cardoso, Thiago Marconi;Machado, Alvaro;Bacellar, Olivia
由巴西利什曼原虫引起的皮肤利什曼病 (CL) 的特点是强烈的 Th1 反应，导致皮肤病变发展。在巴西利什曼原虫传播流行的地区，高达 15% 的健康受试者对可溶性利什曼原虫抗原 (SLA) 迟发型超敏反应检测呈阳性，并被认为患有亚临床 (SC) 感染。 SC 受试者比 CL 患者产生更少的γ干扰素 (IFN-γ) 和肿瘤坏死因子 α (TNF-γ)，但他们能够控制感染。本研究的目的是确定 CD8(+) T 细胞在 SC 感染和 CL 中的作用。用SLA刺激外周血单核细胞(PBMC)，测定CD4(+) IFN-gamma(+)和CD8(+) IFN-gamma(+) T细胞的频率。巴西乳杆菌感染PBMC单核细胞，与CD8+T细胞共培养，测定感染单核细胞的频率、细胞毒性标志物、靶细胞凋亡和颗粒酶B的水平。 SC个体在SLA刺激后CD8(+) IFN-gamma(+)细胞的频率高于CL患者。 SC细胞中感染单核细胞的频率低于CL细胞中的。 CL CD8(+) T 细胞比 SC CD8(+) T 细胞诱导更多的感染单核细胞凋亡。 CL 细胞中 CD8(+) T 细胞的颗粒酶 B 产量高于 SC 细胞。虽然使用颗粒酶 B 抑制剂减少了 CL 组中凋亡细胞的数量，但使用 z-VAD-FMK 对这些细胞的频率没有影响。这些结果表明CL CD8(+) T细胞具有更强的细胞毒性并且可能参与病理学。
Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a strong Th1 response that leads to skin lesion development. In areas where L. braziliensis transmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-gamma) than do CL patients, but they are able to control the infection. The aim of this study was to characterized the role of CD8(+) T cells in SC infection and in CL. Peripheral blood mononuclear cells (PBMC) were stimulated with SLA to determine the frequencies of CD4(+) IFN-gamma(+) and CD8(+) IFN-gamma(+) T cells. Monocytes from PBMC were infected with L. braziliensis and cocultured with CD8(+) T cells, and the frequencies of infected monocytes and levels of cytotoxicity markers, target cell apoptosis, and granzyme B were determined. The frequency of CD8(+) IFN-gamma(+) cells after SLA stimulation was higher for SC individuals than for CL patients. The frequency of infected monocytes in SC cells was lower than that in CL cells. CL CD8(+) T cells induced more apoptosis of infected monocytes than did SC CD8(+) T cells. Granzyme B production in CD8(+) T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8(+) T cells are more cytotoxic and may be involved in pathology.