OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection.
OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection.
复制标题
DOI：
10.4049/jimmunol.1601356
复制
发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Salek-Ardakani S
中科院分区：
文献类型：
--
作者：
Tahiliani V;Hutchinson TE;Abboud G;Croft M;Salek-Ardakani S
t -滤泡辅助细胞（Tfh）和B细胞之间的同源相互作用对于促进保护性抗体反应至关重要。虽然像ICOS这样的共刺激受体被认为是诱导Tfh细胞命运决定的重要因素，但其他分子可能在放大或维持Tfh表型中发挥关键作用。在这里，通过牛痘病毒感染小鼠，我们发现OX40在脾脏白髓中积聚在T:B边界的Tfh细胞上表达，并且OX40依赖的信号直接影响了它们对病毒抗原的反应的大小和质量。Tfh细胞中OX40的缺乏严重损害了生发中心（GC） B细胞表型的获得、浆细胞的产生和病毒特异性Ab反应。最重要的是，我们发现OX40与其配体OX40L之间的持续相互作用，超过了与树突状细胞的初始相遇时间，是维持大量Tfh和GC B细胞持续存在所必需的。有趣的是，OX40在Tfh细胞和GC周围与ICOS共表达，ICOS- icosl相互作用在Tfh和GC B细胞的维持中也同样至关重要。因此，OX40和ICOS以一种合作的、非冗余的方式发挥作用，以最大化和延长急性病毒感染后产生的Tfh反应。
Cognate interactions between T-follicular helper cells (Tfh) and B cells are essential for promoting protective antibody responses. Whereas costimulatory receptors like ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. Here, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T:B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral antigens. OX40 deficiency in Tfh cells profoundly impaired the acquisition of germinal center (GC) B cell phenotype, plasma cell generation, and virus-specific Ab responses. Most significantly, we found that sustained interactions between OX40 and its ligand, OX40L, beyond the time of initial encounter with dendritic cells were required for the persistence of high numbers of Tfh and GC B cells. Interestingly, OX40 was co-expressed with ICOS on Tfh cells in and around the GC, and ICOS-ICOSL interactions were similarly crucial at late times for maintenance of the Tfh and GC B cells. Thus, OX40 and ICOS act in a cooperative, nonredundant manner to maximize and prolong the Tfh response that is generated after acute virus infection.
登录
查看更多内容
DOI：
10.1084/jem.20120219
发表时间：
2012-09-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu X;Yan X;Zhong B;Nurieva RI;Wang A;Wang X;Martin-Orozco N;Wang Y;Chang SH;Esplugues E;Flavell RA;Tian Q;Dong C
通讯作者：
Dong C
DOI：
10.1084/jem.20130592
发表时间：
2013-08-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Byun M;Ma CS;Akçay A;Pedergnana V;Palendira U;Myoung J;Avery DT;Liu Y;Abhyankar A;Lorenzo L;Schmidt M;Lim HK;Cassar O;Migaud M;Rozenberg F;Canpolat N;Aydogan G;Fleckenstein B;Bustamante J;Picard C;Gessain A;Jouanguy E;Cesarman E;Olivier M;Gros P;Abel L;Croft M;Tangye SG;Casanova JL
通讯作者：
Casanova JL
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.4
作者：
Joung, Sun Myung;Park, Zee-Yong;Lee, Joo Young
通讯作者：
Lee, Joo Young