Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells during human hookworm infection modulates antigen-mediated lymphocyte proliferation.
Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells during human hookworm infection modulates antigen-mediated lymphocyte proliferation.
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在人钩虫感染期间，CD4（+）CD25（+）FOXP3（+）调节T细胞的诱导调节抗原介导的淋巴细胞增殖。
DOI：
10.1371/journal.pntd.0001383
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Fujiwara RT
中科院分区：
文献类型：
--
作者：
Ricci ND;Fiúza JA;Bueno LL;Cançado GG;Gazzinelli-Guimarães PH;Martins VG;Matoso LF;de Miranda RR;Geiger SM;Correa-Oliveira R;Gazzinelli A;Bartholomeu DC;Fujiwara RT
钩虫感染被认为是最重要的助长贫穷的被忽视的热带疾病之一，感染了全世界5.76亿至7.4亿人，特别是在热带和亚热带地区。这些吸血线虫具有显著的下调宿主免疫反应的能力，保护自己免受消除并最大限度地减少严重的宿主病理。虽然寄生虫感染的免疫调节可能涉及几种机制，但实验证据表明，慢性感染后，调节性T细胞（T细胞）可能参与下调效应T细胞应答。然而，人类钩虫感染中的T细胞的作用仍然知之甚少，尚未得到解决。在目前的研究中，我们观察到与健康的未感染供体相比，钩虫感染个体的循环CD 4 + CD 25 + FOXP 3+调节性T细胞增加。我们还证明，感染的个体呈现更高水平的表达CTLA-4、GITR、IL-10、TGF-β和IL-17的循环Treg细胞。此外，我们发现钩虫粗抗原刺激减少了感染个体中共表达IL-17的CD 4 + CD 25 + FOXP 3 + T调节细胞的数量。最后，来自感染个体的用排泄/分泌产物或钩虫粗抗原脉冲的PBMC呈现受损的细胞增殖，这部分地通过Treg细胞的耗尽而增强。我们的研究结果表明，调节性T细胞可能在钩虫诱导的免疫抑制中发挥重要作用，有助于感染者钩虫存活的寿命。钩虫感染的特征是寄生虫的长期存活和伴随的宿主免疫调节。在几种可能导致T细胞反应抑制的机制中，我们在这里描述了T调节细胞（也称为Tcells）在人类钩虫感染中的存在和作用。T细胞是CD 4 + T细胞的一个小亚群，也表达特异性细胞标志物，允许其进一步鉴定（CD 25和FOXP 3）。我们的研究结果表明，钩虫感染诱导外周血中的T细胞增多，随后是表达与细胞调节相关的几种标志物和细胞因子（CTLA-4、GITR、IL-10、TGF-β和IL-17）的更高水平的循环Treg细胞。我们还证明，在体外消耗THBE部分增强自然受损的细胞增殖的淋巴细胞从感染的个人抗原刺激后。我们的研究结果表明，调节性T细胞可能在钩虫诱导的免疫抑制中发挥重要作用，有助于感染者钩虫存活的寿命。
Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4+CD25+FOXP3+ regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-β and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4+CD25+FOXP3+ T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people. The hookworm infection is characterized by the long-term survival of the parasite and the concomitant modulation of the host immunity. Among several mechanisms that may account for the suppression of T cell response, we here described the presence and role of T regulatory cells (also known as Tregs) in the human hookworm infection. Tregs are a minor subpopulation of CD4+ T-cells, which also express specific cell markers that allow its further identification (CD25 and FOXP3). Our results showed that hookworm infection induce an augmentation of Tregs in the peripheral blood, followed by the higher levels of circulating Treg cells expressing several markers and cytokines associated with cell regulation (CTLA-4, GITR, IL-10, TGF-β and IL-17). We also demonstrated that in vitro depletion of Tregs partially enhanced the naturally impaired cellular proliferation of lymphocytes from infected individuals after antigenic stimulation. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people.
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影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
DOI：
10.4049/jimmunol.181.4.2414
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elliott DE;Metwali A;Leung J;Setiawan T;Blum AM;Ince MN;Bazzone LE;Stadecker MJ;Urban JF Jr;Weinstock JV
通讯作者：
Weinstock JV
影响因子：
4.8
作者：
Bethony, J;Loukas, A;Hotez, PJ
通讯作者：
Hotez, PJ
影响因子：
30.5
作者：
Fallarino, F;Grohmann, U;Puccetti, P
通讯作者：
Puccetti, P
DOI：
10.1084/jem.188.10.1849
发表时间：
1998-11-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Wahl SM
通讯作者：
Wahl SM