Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions.
Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions.
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DOI：
10.4049/jimmunol.1303460
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
Badovinac VP
中科院分区：
文献类型：
--
作者：
Duong S;Condotta SA;Rai D;Martin MD;Griffith TS;Badovinac VP
脓毒症的死亡率通常由继发感染引起，脓毒症影响病原体特异性记忆CD 8 T细胞应答的程度仍然未知。使用盲肠结扎穿孔（CLP）模型的多微生物脓毒症，我们观察到快速凋亡的预先存在的记忆CD 8 T细胞脓毒症诱导后，导致损失的CD 8 T细胞介导的保护。脓毒症后记忆性CD 8 T细胞的Ag敏感性（功能性亲和力）和Ag驱动的二次扩增降低，进一步导致观察到的CD 8 T细胞介导的免疫力丧失。此外，在脓毒症诱导后早期，记忆性CD 8 T细胞对异源感染的非Ag依赖性旁观者激活也显著受损。在近交系和远交系宿主中观察到预先存在的记忆性CD 8 T细胞对感知炎症和通过IFN-γ产生对异源性感染的应答的敏感性降低，并且由外在（而非细胞内在）因素控制，这表明脓毒症诱导的环境变化调节记忆性CD 8 T细胞的先天功能。总之，本研究中的数据揭示了脓毒症在塑造感染或疫苗诱导的记忆CD 8 T细胞的数量和功能方面的先前未被认识到的作用，并将有助于进一步确定脓毒症诱导的免疫抑制阶段T细胞介导的免疫力下降。
Mortality from sepsis frequently results from secondary infections, and the extent to which sepsis affects pathogen-specific memory CD8 T cell responses remains unknown. Using the cecal-ligation and puncture (CLP) model of polymicrobial sepsis, we observed rapid apoptosis of pre-existing memory CD8 T cells after sepsis induction that led to a loss in CD8 T cell-mediated protection. Ag-sensitivity (functional avidity) and Ag-driven secondary expansion of memory CD8 T cells were decreased after sepsis, further contributing to the observed loss in CD8 T cell-mediated immunity. Moreover, Ag-independent bystander activation of memory CD8 T cells in response to heterologous infection was also significantly impaired early after sepsis induction. The reduced sensitivity of pre-existing memory CD8 T cells to sense inflammation and respond to heterologous infection by IFN-γ production was observed in inbred and outbred hosts and controlled by extrinsic (but not cell intrinsic) factors suggesting that sepsis-induced changes in the environment regulates innate functions of memory CD8 T cells. Taken together, the data in this study revealed a previously unappreciated role of sepsis in shaping the quantity and functionality of infection- or vaccine-induced memory CD8 T cells and will help further define the decline in T cell-mediated immunity during the sepsis-induced phase of immunosuppression.
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DOI：
10.4049/jimmunol.1101180
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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发表时间：
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期刊：
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8.8
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DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
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影响因子：
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影响因子：
82.9
作者：
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通讯作者：
Harty, JT