Activation and exhaustion of antigen-specific CD8+ T cells occur in different splenic compartments during infection with Plasmodium berghei.

Activation and exhaustion of antigen-specific CD8+ T cells occur in different splenic compartments during infection with Plasmodium berghei.
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在伯氏疟原虫感染期间,抗原特异性 CD8 T 细胞的激活和耗竭发生在不同的脾室中。

DOI:
10.1016/j.parint.2017.01.022
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发表时间:
2017
期刊:
影响因子:
1.9
通讯作者:
Yui K
Yui K
中科院分区:
医学3区
文献类型:
--
作者:
1.Bayarsaikhan G;Miyakoda M;Yamamoto K;Kimura D;Akbari M;Yuda M;Yui K

文献摘要

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脾脏是T细胞在疟疾寄生虫感染过程中启动的主要器官。然而,很少有人知道的动态免疫反应和它们的定位在脾组织在疟疾感染。我们使用表达模型抗原卵清蛋白(OVA)蛋白的重组寄生虫检测了伯氏疟原虫感染过程中小鼠CD 8 +T细胞的应答,并将其与表达相同抗原的李斯特菌引起的应答进行了比较。在疟疾感染期间,OVA特异性CD 8 +T细胞主要在脾脏的白色髓中活化,与李斯特菌感染期间观察到的相似。然而,这些活化的CD 8 +T细胞的命运是不同的。在疟疾寄生虫感染期间,活化的CD 8 +T细胞优先积累在红髓和/或边缘区,其中OVA特异性CD 8 +T细胞的细胞因子产生减少,多种抑制性受体的表达增加。这些细胞优先发生凋亡,表明T细胞耗竭主要发生在红髓和/或边缘区。然而,在李斯特菌感染期间,OVA特异性CD 8 +T细胞仅在白色牙髓中瞬时表达抑制性受体,并保持其产生细胞因子和成为记忆细胞的能力。这些结果强调了CD 8 +T细胞在疟原虫和李斯特菌感染过程中的不同命运,并表明在疟原虫感染过程中,特异性CD 8 +T细胞的激活和耗竭发生在不同的脾脏隔室中。
The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8+T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeriamonocytogenesexpressing the same antigen. OVA-specific CD8+T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8+T cells were distinct. During infection with malaria parasites, activated CD8+T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8+T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8+T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8+T cells during infection withPlasmodiumparasites and Listeria, and suggested that activation and exhaustion of specific CD8+T cells occurred in distinct spleen compartments during infection with malaria parasites.