Magnitude and Kinetics of T Cell and Antibody Responses During H1N1pdm09 Infection in Inbred Babraham Pigs and Outbred Pigs.

Magnitude and Kinetics of T Cell and Antibody Responses During H1N1pdm09 Infection in Inbred Babraham Pigs and Outbred Pigs.
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DOI:
10.3389/fimmu.2020.604913
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发表时间:
2020
影响因子:
7.3
通讯作者:
Tchilian E
Tchilian E
中科院分区:
医学2区
文献类型:
--
作者:
Edmans M;McNee A;Porter E;Vatzia E;Paudyal B;Martini V;Gubbins S;Francis O;Harley R;Thomas A;Burt R;Morgan S;Fuller A;Sewell A;Charleston B;Bailey M;Tchilian E

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我们使用猪(一种与人类具有许多生理相似性的大型流感天然宿主动物)来表征对2009年大流行性H1N1病毒感染的αβ、γδ T细胞和抗体(Ab)免疫应答。我们评估了具有相同MHC(猪白细胞抗原)的近交系Babraham猪的病毒感染动力学和相关反应,并将其与商业远交动物进行了比较。高水平的鼻病毒脱落持续至感染后第4至5天,随后在第9天急剧下降并清除病毒。从感染后第5至6天可检测到适应性T细胞和Ab应答,在第9至14天达到峰值。γδ T细胞在感染后第2天离体产生细胞因子,而从感染后第7天检测到病毒反应性IFNγ产生γδ T细胞。对血液、肺、肺引流淋巴结和支气管肺泡灌洗(BAL)中NP四聚体特异性和病毒特异性CD8和CD4 T细胞的分析显示,这些组织之间细胞因子产生存在明显差异。BAL含有最高度活化的CD8、CD4和γδ T细胞,产生大量细胞因子,这可能有助于消除病毒。血液中的弱反应并不反映强的局部肺免疫反应。在H1N1pdm09流感感染后,Babraham猪的免疫应答与远系繁殖动物的免疫应答相当。同时利用这两种猪模型的能力将为分析对流感的免疫反应提供无与伦比的能力。
We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to days 4 to 5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from days 5 to 6 post infection reaching a peak at 9 to 14 days. γδ T cells produced cytokines ex vivo at day 2 post infection, while virus reactive IFNγ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes, and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4, and γδ T cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyze immune responses to influenza.
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