IL-4-secreting secondary T follicular helper (Tfh) cells arise from memory T cells, not persisting Tfh cells, through a B cell-dependent mechanism.
IL-4-secreting secondary T follicular helper (Tfh) cells arise from memory T cells, not persisting Tfh cells, through a B cell-dependent mechanism.
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DOI：
10.4049/jimmunol.1401225
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Pearce EJ
中科院分区：
文献类型：
--
作者：
Fairfax KC;Everts B;Amiel E;Smith AM;Schramm G;Haas H;Randolph GJ;Taylor JJ;Pearce EJ
体液免疫需要滤泡辅助性T细胞（Tfh）和B细胞之间的相互作用。然而，对于二次免疫应答过程中这种细胞间相互作用缺乏详细的了解。我们通过关注对一种可溶的、无佐剂的、病原体衍生的抗原（SEA）的应答来研究这一问题，该抗原可诱导2型免疫。我们发现，在初次免疫后，活化的Tfh细胞在生发中心内长期存在。然而，二次应答的强度似乎并不依赖于预先存在的Tfh细胞。相反，Tfh细胞群通过一个依赖于被招募到反应性淋巴结的记忆T细胞以及B细胞参与的过程而扩增。我们发现在二次应答过程中，白细胞介素 - 4（IL - 4）对于一群浆母细胞的扩增至关重要，这与SEA特异性IgG1滴度的升高相关。此外，在用SEA免疫后（但在用诱导1型免疫的抗原免疫时不会），IL - 4和IL - 21由单个Tfh细胞共同产生，揭示了一种潜在的机制，通过该机制适当的类别转换可与浆母细胞增殖相耦合以增强2型免疫。我们的研究结果表明，在二次Th2应答过程中，IL - 4在T细胞和B细胞之间的相互作用中起着关键作用，这对疫苗设计具有重要意义。
Humoral immunity requires crosstalk between T follicular helper (Tfh) and B cells. Nevertheless, a detailed understanding of this intercellular interaction during secondary immune responses is lacking. We examined this by focusing on the response to a soluble, unadjuvanted, pathogen-derived Ag (SEA) that induces type 2 immunity. We found that activated Tfh cells persisted for long periods within germinal centers following primary immunization. However, the magnitude of the secondary response appeared not to depend on pre-existing Tfh cells. Instead, Tfh cell populations expanded through a process dependent on memory T cells recruited into the reactive LN, and the participation of B cells. We found that during the secondary response, IL-4 was critical for the expansion of a population of plasmablasts that correlated with increased SEA-specific IgG1 titers. Additionally, following immunization with SEA (but not with an Ag that induced type 1 immunity), IL-4 and IL-21 were co-produced by individual Tfh cells, revealing a potential mechanism through which appropriate class-switching can be coupled to plasmablast proliferation to enforce type 2 immunity. Our findings demonstrate a pivotal role for IL-4 in the interplay between T and B cells during a secondary Th2 response and have significant implications for vaccine design.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
DOI：
10.4049/jimmunol.1301284
发表时间：
2014-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barnett LG;Simkins HM;Barnett BE;Korn LL;Johnson AL;Wherry EJ;Wu GF;Laufer TM
通讯作者：
Laufer TM
影响因子：
3.6
作者：
Gigoux, Mathieu;Lovato, Amanda;Suh, Woong-Kyung
通讯作者：
Suh, Woong-Kyung
影响因子：
6.7
作者：
Fairfax KC;Amiel E;King IL;Freitas TC;Mohrs M;Pearce EJ
通讯作者：
Pearce EJ
影响因子：
32.4
作者：
Baumjohann, Dirk;Preite, Silvia;Sallusto, Federica
通讯作者：
Sallusto, Federica