The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion.
The Chronic Stages of Bovine Fasciola hepatica Are Dominated by CD4 T-Cell Exhaustion.
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牛fasciola Hepatica的慢性阶段以CD4 T细胞耗尽为主。
DOI：
10.3389/fimmu.2017.01002
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发表时间：
2017
影响因子：
7.3
通讯作者：
Flynn RJ
中科院分区：
文献类型：
--
作者：
Sachdev D;Gough KC;Flynn RJ
反刍动物的肝片形吸虫感染导致慢性感染，随着开放的发展，转变为TGF-β和IL-10主导的应答。在这里，我们探讨CD4 t细胞在主要引流淋巴结内的反应。我们发现Foxp3在CD4细胞中表达极低，但在γδ (WC1+)群体中表达水平升高。在肝淋巴结（HLN）内存在一种强烈的t细胞内在衰竭表型，其特征是缺乏抗原特异性增殖和细胞因子分泌。从HLN中恢复的CD4 t细胞PD-1表达水平高，IL-2分泌水平低。外源性IL-2部分修复了这一缺陷；联合中和IL-10和TGF-β，可完全恢复细胞增殖和细胞因子的产生。此外，促进这种调节的机制明显不耦合，寄生虫特异性增殖和细胞因子分泌由独立手段控制。这些数据表明，在慢性感染早期存在CD4 t细胞的内在调节，可能导致抵抗再感染的失败。
Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1+) population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN) characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection.
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影响因子：
3.7
作者：
Nishimori A;Konnai S;Okagawa T;Maekawa N;Ikebuchi R;Goto S;Sajiki Y;Suzuki Y;Kohara J;Ogasawara S;Kato Y;Murata S;Ohashi K
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影响因子：
2.4
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Codner, G. F.;Stear, M. J.;Ellis, S. A.
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影响因子：
4.3
作者：
Flynn, R. J.;Mulcahy, G.;McNair, J.
通讯作者：
McNair, J.
影响因子：
4.4
作者：
Hoek, Aad;Rutten, Victor P. M. G.;Koets, Ad P.
通讯作者：
Koets, Ad P.
影响因子：
3.8
作者：
Fu Y;Chryssafidis AL;Browne JA;O'Sullivan J;McGettigan PA;Mulcahy G
通讯作者：
Mulcahy G