The initial draining lymph node primes the bulk of the CD8 T cell response and influences memory T cell trafficking after a systemic viral infection.
The initial draining lymph node primes the bulk of the CD8 T cell response and influences memory T cell trafficking after a systemic viral infection.
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DOI：
10.1371/journal.ppat.1003054
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Varga SM
中科院分区：
文献类型：
--
作者：
Olson MR;McDermott DS;Varga SM
淋巴细胞性脉络丛脑膜炎病毒（LCMV）引起小鼠全身感染，病毒复制发生在外周组织和次级淋巴器官。由于病毒的快速全身传播，负责诱导lcmv特异性CD8 T细胞反应的次级淋巴器官定义不清。我们发现纵隔淋巴结（MedLN）是LCMV感染后的主要引流淋巴结。此外，我们证明MedLN负责启动大多数病毒特异性CD8 T细胞反应。急性感染消退后，引流的MedLN表现出反应性淋巴结的特征，包括生发中心B细胞的增加和感染后长达60天的细胞数量增加。此外，与非引流淋巴结相比，反应性MedLN含有CD62L -效应记忆CD8 T细胞的频率增加。LCMV特异性CD62L -记忆性CD8 T细胞在MedLN中的积累与残留抗原无关，并不是MedLN的独特特征，因为LCMV足垫感染会导致类似的病毒特异性CD62L -效应性记忆性CD8 T细胞在腘窝引流淋巴结中的增加。我们的研究结果表明，CD62L−效应记忆CD8 T细胞在感染解决后的较长时间内优先进入引流淋巴结。在急性病毒感染后，需要CD8 T细胞来清除受感染的宿主细胞。此外，记忆性CD8 T细胞为宿主提供抗继发性感染的免疫力。关于CD8 T细胞对诱导局部感染的病毒的启动已经知道很多，但是在全身性病毒感染后负责启动大多数CD8 T细胞的位点仍然不清楚。淋巴细胞性脉络丛脑膜炎病毒（LCMV）腹腔接种可诱导急性全身性病毒感染，引发强烈的CD8 T细胞应答。尽管腹腔内LCMV感染导致快速的全身病毒复制，但我们证明纵隔淋巴结（MedLN）作为初始引流淋巴结，代表了诱导急性CD8 T细胞反应的主要部位。此外，我们观察到CD62L−效应记忆CD8 T细胞在LCMV感染后优先被招募到引流的MedLN中长达60天。总的来说，这些研究表明，在原发性感染后，引流淋巴结在很长一段时间内保持着保护宿主免受病原体二次感染的状态。
Lymphocytic choriomeningitis virus (LCMV) causes a systemic infection in mice with virus replication occurring in both peripheral tissues and secondary lymphoid organs. Because of the rapid systemic dissemination of the virus, the secondary lymphoid organs responsible for the induction of the LCMV-specific CD8 T cell response are poorly defined. We show that the mediastinal lymph node (MedLN) serves as the primary draining lymph node following LCMV infection. In addition, we demonstrate that the MedLN is responsible for priming the majority of the virus-specific CD8 T cell response. Following resolution of the acute infection, the draining MedLN exhibits characteristics of a reactive lymph node including an increased presence of germinal center B cells and increased cellularity for up to 60 days post-infection. Furthermore, the reactive MedLN harbors an increased frequency of CD62L− effector memory CD8 T cells as compared to the non-draining lymph nodes. The accumulation of LCMV-specific CD62L− memory CD8 T cells in the MedLN is independent of residual antigen and is not a unique feature of the MedLN as footpad infection with LCMV leads to a similar increase of virus-specific CD62L− effector memory CD8 T cells in the draining popliteal lymph node. Our results indicate that CD62L− effector memory CD8 T cells are granted preferential access into the draining lymph nodes for an extended time following resolution of an infection. CD8 T cells are required for the elimination of infected host cells following an acute virus infection. In addition, memory CD8 T cells provide immunity to the host against a secondary infection. Much is known about the priming of CD8 T cells towards viruses that induce a localized infection, however the site responsible for priming the majority of CD8 T cells following a systemic viral infection remains unclear. Lymphocytic choriomeningitis virus (LCMV) induces an acute systemic viral infection when inoculated intraperitoneally, eliciting a robust CD8 T cell response. Although intraperitoneal LCMV infection results in rapid systemic viral replication, we demonstrate that the mediastinal lymph node (MedLN) serves as the initial draining lymph node and represents the primary site for the induction of the acute CD8 T cell response. In addition, we observe that CD62L− effector memory CD8 T cells are preferentially recruited into the draining MedLN for up to 60 days following LCMV infection. Collectively, these studies indicate that the draining lymph node remains poised to defend the host against a secondary encounter with a pathogen for a prolonged time following the primary infection.
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DOI：
10.1084/jem.20011502
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Campbell DJ;Butcher EC
通讯作者：
Butcher EC
影响因子：
4.4
作者：
Manfredi, Angelo A.;Capobianco, Annalisa;Del Maschiot, Alessandro
通讯作者：
Del Maschiot, Alessandro
影响因子：
4.4
作者：
Jelley-Gibbs, Dawn M.;Dibble, John P.;Swain, Susan L.
通讯作者：
Swain, Susan L.
影响因子：
2.4
作者：
MARCO, AJ;DOMINGO, M;DOMINGUEZ, L
通讯作者：
DOMINGUEZ, L
DOI：
10.1084/jem.185.8.1493
发表时间：
1997-04-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McEvoy LM;Sun H;Frelinger JG;Butcher EC
通讯作者：
Butcher EC