Spatial alterations between CD4(+) T follicular helper, B, and CD8(+) T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape.
Spatial alterations between CD4(+) T follicular helper, B, and CD8(+) T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape.
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DOI：
10.4049/jimmunol.1103138
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Villinger F
中科院分区：
文献类型：
--
作者：
Hong JJ;Amancha PK;Rogers K;Ansari AA;Villinger F
HIV/SIV感染诱导慢性免疫激活，伴淋巴结构重塑和高γ -球蛋白血症，尽管导致这些症状的机制仍未完全阐明。此外，淋巴结已被强调为SIV在体内逃逸的偏爱部位。研究人员对20只感染SIVmac239的恒河猴进行了观察，观察它们从前期感染到急性和慢性感染的进展，首次记录了T滤泡辅助细胞（TFH）和B细胞的局部动态。SIV感染的进展伴随着含有生发中心（GCs）和TFH细胞的清晰描绘的卵泡数量的增加，淋巴结中PD-1表达密度的逐渐增加。PD-1+ TFH细胞的增加伴随着GCs内Ki67+ B细胞的大量积累。然而，与血液不同的是，在淋巴结中观察到CD27+记忆B细胞的频率显著增加，表明这些细胞的周转增加，与总抗体和SIV特异性抗体水平的增加相关。重要的是，与T细胞区相比，GCs似乎排除了CD8+ T细胞，同时容纳了越来越多的CD4+ T细胞，其中许多细胞对SIVgag呈阳性，为病毒复制和储存库提供了特别有利的环境。我们的数据首次强调了SIV感染期间GC细胞亚群的重要空间相互作用，淋巴组织维持循环B细胞亚群相对稳定水平的能力，以及SIV感染期间GC内病毒库的潜在机制。
HIV/SIV infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. Moreover, lymph nodes have been highlighted as a predilection site for SIV escape in vivo. Following 20 rhesus macaques infected with SIVmac239, as they progress from pre to acute and chronic infection, we document for the first time the local dynamics T follicular helper (TFH) cells and B cells in situ. Progression of SIV infection was accompanied with increased numbers of well delineated follicles containing germinal centers (GCs) and TFH cells with a progressive increase in the density of PD-1 expression in lymph nodes. The rise in PD-1+ TFH cells was followed by a substantial accumulation of Ki67+ B cells within GCs. However, unlike in blood, major increases in the frequency of CD27+ memory B cells were observed in lymph nodes, indicating increased turnover of these cells, correlated with increases in total and SIV specific antibody levels. Of importance, compared to T cell zones, GCs seemed to exclude CD8+ T cells while harboring increasing numbers of CD4+ T cells, many of which are positive for SIVgag, providing an environment particularly beneficial for virus replication and reservoirs. Our data highlight for the first time important spatial interactions of GC cell subsets during SIV infection, the capacity of lymphoid tissues to maintain stable relative levels of circulating B cell subsets and a potential mechanism for viral reservoirs within GCs during SIV infection.
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影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
通讯作者：
Dong, Chen
DOI：
10.1038/nri2524
发表时间：
2009-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.3
作者：
Moir, Susan;Ho, Jason;Fauci, Anthony S.
通讯作者：
Fauci, Anthony S.
影响因子：
0.7
作者：
Folks, T;Rowe, T;Ansari, AA
通讯作者：
Ansari, AA
影响因子：
4.4
作者：
Haynes, Nicole M.;Allen, Christopher D. C.;Cyster, Jason G.
通讯作者：
Cyster, Jason G.