Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis.
Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis.
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DOI：
10.1371/journal.ppat.1010296
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发表时间：
2022-06
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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初始的TCR参与（启动）幼稚CD8+ T细胞导致T细胞扩增，这些早期事件影响不同效应和记忆群体的产生。在感染期间，活化的T细胞可以再次遇到同源抗原，但这些事件如何影响局部效应反应或记忆群体的形成尚不清楚。为了解决这个问题，我们将表达TCR激活的Nur77-GFP报告基因的OT-I T细胞与表达OVA的弓形虫配对，以评估与抗原的二次接触如何影响CD8+ T细胞的反应。在急性感染期间，受感染组织的TCR刺激与寄生虫负荷相关，并与效应细胞标记物相关，而Nur77-GFP- OT-I表现出效应记忆电位的迹象。然而，急性感染小鼠的Nur77-GFP-和Nur77-GFP+ OT-I在转移到幼稚小鼠时形成了相似的记忆群体。在中枢神经系统感染的慢性阶段，TCR激活与大规模的转录变化、效应T细胞表型的获得以及CD103+ CD69+ Trm样细胞群的产生有关。虽然抑制寄生虫复制导致效应反应减少，但没有改变Trm种群。这些数据集强调，最近的TCR激活有助于CD8+ T细胞反应的表型异质性，但表明这一过程对急性和慢性感染阶段的记忆群体的影响有限。启动后，效应CD8+ T细胞识别I类限制性微生物抗原的能力对控制许多急性和慢性感染非常重要。然而，最近的T细胞受体刺激在正在进行的T细胞反应形成中的作用尚不清楚。在这里，我们利用TCR刺激的遗传报告，高参数流式细胞术和成像来表征急性和慢性感染时外周和中枢神经系统对弓形虫寄生虫TCR驱动的病原体特异性T细胞反应的表型。这些数据集强调了最近的TCR激活对CD8+ T细胞反应表型异质性的贡献，但表明T细胞记忆的形成和维持独立于最近的TCR激活。
Initial TCR engagement (priming) of naive CD8+ T cells results in T cell expansion, and these early events influence the generation of diverse effector and memory populations. During infection, activated T cells can re-encounter cognate antigen, but how these events influence local effector responses or formation of memory populations is unclear. To address this issue, OT-I T cells which express the Nur77-GFP reporter of TCR activation were paired with the parasite Toxoplasma gondii that expresses OVA to assess how secondary encounter with antigen influences CD8+ T cell responses. During acute infection, TCR stimulation in affected tissues correlated with parasite burden and was associated with markers of effector cells while Nur77-GFP- OT-I showed signs of effector memory potential. However, both Nur77-GFP- and Nur77-GFP+ OT-I from acutely infected mice formed similar memory populations when transferred into naive mice. During the chronic stage of infection in the CNS, TCR activation was associated with large scale transcriptional changes and the acquisition of an effector T cell phenotype as well as the generation of a population of CD103+ CD69+ Trm like cells. While inhibition of parasite replication resulted in reduced effector responses it did not alter the Trm population. These data sets highlight that recent TCR activation contributes to the phenotypic heterogeneity of the CD8+ T cell response but suggest that this process has a limited impact on memory populations at acute and chronic stages of infection. Following priming, the ability of effector CD8+ T cells to recognize class I restricted microbial antigens is important to control many acute and chronic infections. However the role that recent T cell receptor stimulation plays in the formation of ongoing T cell responses is unclear. Here, we utilize a genetic reporter of TCR stimulation, high parameter flow cytometry, and imaging to characterize TCR-driven phenotypes of pathogen specific T cell responses to the parasite Toxoplasma gondii during acute and chronic infection in the periphery and central nervous system. These data sets highlight the contribution of recent TCR activation on the phenotypic heterogeneity of the CD8+ T cell response but suggest that T cell memory formation and maintenance is independent of recent TCR activation.
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DOI：
10.1084/jem.20031051
发表时间：
2003-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Berg RE;Crossley E;Murray S;Forman J
通讯作者：
Forman J
影响因子：
8.8
作者：
Chu T;Tyznik AJ;Roepke S;Berkley AM;Woodward-Davis A;Pattacini L;Bevan MJ;Zehn D;Prlic M
通讯作者：
Prlic M
DOI：
10.1084/jem.20201314
发表时间：
2021-11-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Frickel EM;Hunter CA
通讯作者：
Hunter CA
影响因子：
7.3
作者：
Netherby-Winslow CS;Ayers KN;Lukacher AE
通讯作者：
Lukacher AE
影响因子：
30.5
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