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人内脏利什曼病中 CD8 T 细胞耗竭。

CD8 T cell exhaustion in human visceral leishmaniasis.

机构信息

Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

出版信息

J Infect Dis. 2014 Jan 15;209(2):290-9. doi: 10.1093/infdis/jit401. Epub 2013 Aug 6.


DOI:10.1093/infdis/jit401
PMID:23922369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3873784/
Abstract

Little is known about CD8 T cells in human visceral leishmaniasis (VL) and it is unclear if these cells have a protective, pathological and/or suppressive function. In experimental VL CD8 T cells have been shown to contribute to parasite control and play an important role in vaccine-generated immunity. To better understand the role of CD8 T cells in human VL, we examined molecules associated with anergy and cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) and splenic aspirates (SA), and in CD8 cells derived from these tissues. Gene and surface marker expression suggest that splenic CD8 cell predominantly display an anergic phenotype, whereas CD8-PBMC have features of both anergic cells and CTLs. CD8 cells contribute to the baseline IFNγ levels in whole blood (WB) and SA cultures, but not to the Leishmania induced IFNγ release that is revealed using WB cultures. Blockade of CTLA-4 or PD1 had no effect on IFNγ production or parasite survival in SA cultures. Following cure, CD8 T cells contribute to the Leishmania induced IFNγ production observed in Leishmania stimulated cell cultures. We suggest CD8 T cells are driven to anergy/exhaustion in human VL, which affect their ability to contribute to protective immune responses.

摘要

关于人类内脏利什曼病(VL)中的 CD8 T 细胞知之甚少,目前尚不清楚这些细胞是否具有保护、病理性和/或抑制功能。在实验性 VL 中,CD8 T 细胞已被证明有助于寄生虫控制,并在疫苗产生的免疫中发挥重要作用。为了更好地了解 CD8 T 细胞在人类 VL 中的作用,我们检查了与外周血单核细胞(PBMC)和脾抽吸物(SA)中的无反应性和细胞毒性 T 淋巴细胞(CTL)相关的分子,以及源自这些组织的 CD8 细胞中的这些分子。基因和表面标记物的表达表明,脾 CD8 细胞主要表现出无反应性表型,而 CD8-PBMC 具有无反应性细胞和 CTL 的特征。CD8 细胞有助于全血(WB)和 SA 培养物中的基础 IFNγ 水平,但不能促进使用 WB 培养物揭示的利什曼原虫诱导的 IFNγ 释放。阻断 CTLA-4 或 PD1 对 SA 培养物中的 IFNγ 产生或寄生虫存活没有影响。治愈后,CD8 T 细胞有助于在利什曼原虫刺激的细胞培养物中观察到的利什曼原虫诱导的 IFNγ 产生。我们认为,在人类 VL 中,CD8 T 细胞被驱动至无反应/衰竭状态,这影响了它们对保护性免疫反应的贡献能力。

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本文引用的文献

[1]
CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis.

J Invest Dermatol. 2013-1-15

[2]
IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis.

J Infect Dis. 2011-10-1

[3]
Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients.

PLoS Negl Trop Dis. 2011-5-31

[4]
Interferon-gamma release assay (modified QuantiFERON) as a potential marker of infection for Leishmania donovani, a proof of concept study.

PLoS Negl Trop Dis. 2011-4-19

[5]
IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis.

J Immunol. 2011-2-28

[6]
Differential in vitro CD4+/CD8+ T-cell response to live vs. killed Leishmania major.

Parasite Immunol. 2010-2

[7]
B7-H1 blockade increases survival of dysfunctional CD8(+) T cells and confers protection against Leishmania donovani infections.

PLoS Pathog. 2009-5

[8]
Acquisition of polyfunctionality by Epstein-Barr virus-specific CD8+ T cells correlates with increased resistance to galectin-1-mediated suppression.

J Virol. 2009-6

[9]
Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade.

PLoS Pathog. 2009-2

[10]
Could the lower frequency of CD8+CD18+CD45RO+ lymphocytes be biomarkers of human VL?

Int Immunol. 2009-2

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