IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.
IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.
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DOI：
10.4049/jimmunol.1601119
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Swain SL
中科院分区：
文献类型：
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作者：
Brahmakshatriya V;Kuang Y;Devarajan P;Xia J;Zhang W;Vong AM;Swain SL
幼稚CD 4 T细胞应答，特别是它们帮助B细胞应答的能力，随着年龄的增长而受到损害。我们发现，使用用TLR激动剂、polyI：C和CpG离体预处理的APC在体内引发初始CD 4 T细胞，恢复它们扩增并成为生发中心T滤泡辅助细胞的能力，并增强B细胞IgG抗体产生。增强的辅助应答依赖于激活的APC产生的IL-6。与年轻人相比，老年人的幼稚CD 4 T细胞对IL-6的应答次优，使得需要更高的剂量来诱导相当的信号传导。预激活APC克服了这一缺陷。年轻的CD 4 T细胞的反应也通过具有类似效果但仅具有部分IL-6依赖性的预活化APC而增强。引人注目的是，仅将活化的APC引入老年小鼠显著增强了灭活流感疫苗的抗体产生。这些发现揭示了APC在产生有效的CD 4 T细胞帮助的初始同源相互作用期间产生IL-6的核心作用，其随着年龄的增长而变得更大。在没有APC活化的情况下，老化的CD 4 T细胞应答向IL-6非依赖性Th 1和ThCTL应答转变。因此，特异性激活APC并为其提供抗原的策略可能会增强疫苗应答中Ab介导的保护作用。
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pre-treated ex vivo with TLR agonists, polyI:C and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG antibody production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond sub-optimally to IL-6 compared to the young, such that higher doses are required to induce comparable signaling. Pre-activating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by pre-activating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised antibody production to inactivated influenza vaccine. These findings reveal a central role for production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation aging CD4 T cell responses shift towards IL-6-independent Th1 and ThCTL responses. Thus, strategies that specifically activate and provide antigen to APC could potentially enhance Ab mediated protection in vaccine responses.