Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo.
Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo.
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DOI：
10.7554/elife.06994
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发表时间：
2015-08-10
期刊：
影响因子：
7.7
通讯作者：
Brewer JM
中科院分区：
文献类型：
--
作者：
Benson RA;MacLeod MK;Hale BG;Patakas A;Garside P;Brewer JM
B细胞产生高亲和力的类转换抗体取决于T滤泡辅助细胞（Tfh）的有效分化。在这里，我们定义条件具体加强Tfh分化和提供保护的流感感染模型。Tfh反应与树突状细胞（DC）的抗原呈递时间延长有关，树突状细胞（DC）将T细胞/DC相互作用维持到激活的第3阶段（bb0 - 72小时）。阻断第3阶段相互作用可消除Tfh代，证明T细胞dc行为与功能结果之间存在因果关系。因此，目前的数据解释了抗原呈递的持续时间如何影响T细胞- dc相互作用的动力学，从而决定Tfh细胞在发展中的免疫反应中的分化。DOI: http://dx.doi.org/10.7554/eLife.06994.001免疫系统保护身体免受感染、癌症和其他疾病的侵害。入侵的微生物和癌细胞表现出通常在身体健康细胞中找不到的蛋白质。这些分子的片段——被称为抗原——可能被免疫系统检测到，然后免疫系统会产生抗体和其他反应，试图摧毁这种威胁。抗体是由一种免疫细胞（称为B细胞）在另一种称为滤泡辅助T细胞（Tfh）的细胞的帮助下产生的。在免疫应答过程中，Tfh细胞由之前没有遇到抗原的naïve T细胞形成。这个过程有几个阶段，当naïve T细胞与树突状细胞和其他免疫细胞表面的抗原相互作用时，这个过程就被激活了。然而，目前还不清楚这个过程是如何运作的。这里，Benson等人研究了小鼠对不同大小抗原的Tfh细胞的形成。实验表明，树突状细胞显示较大抗原的时间比显示较小抗原的时间长。小抗原和大抗原都允许树突状细胞与T细胞相互作用。然而，只有显示较大抗原的树突状细胞与T细胞保持较长时间的相互作用（进入Tfh细胞形成的最后阶段）。这增强了Tfh细胞的产生，从而促进了针对抗原的抗体的产生，从而产生对感染的免疫力。进一步的实验发现，在Tfh细胞形成的最后阶段，阻断树突状细胞和T细胞之间的相互作用会减少Tfh细胞的产生。Benson等人的研究结果表明，树突状细胞在其表面呈递抗原的时间长度影响Tfh细胞的产生和随后的免疫反应。由于Tfh细胞对于形成针对病毒的持久免疫力至关重要，因此这些发现可能有助于开发更有效的流感和其他疾病疫苗。DOI: http://dx.doi.org/10.7554/eLife.06994.002
The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (>72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response. DOI: http://dx.doi.org/10.7554/eLife.06994.001 The immune system protects the body from infections, cancer and other diseases. Invading microbes and cancerous cells exhibit proteins that are not normally found in the healthy cells of the body. Fragments of these molecules—known as antigens—may be detected by the immune system, which can then respond by producing antibodies and other responses that try to destroy the threat. Antibodies are produced by one type of immune cell (known as B cells) with the help of other cells called follicular helper T (Tfh) cells. During an immune response, Tfh cells form from ‘naïve’ T cells that have not encountered an antigen before. This process has several stages and is activated when the naïve T cells interact with antigens that are displayed on the surface of dendritic cells and other immune cells. However, it is not clear exactly how this process works. Here, Benson et al. studied the formation of Tfh cells in mice in response to antigens of different sizes. The experiments show that the dendritic cells displayed larger antigens for longer periods of time than they displayed the smaller antigens. Both the small and large antigens allowed dendritic cells to interact with T cells. However, only the dendritic cells that displayed the larger antigens maintained the interaction with T cells for longer periods of time (into the last stage of Tfh cell formation). This enhanced the production of Tfh cells, which boosted the production of antibodies against the antigens to generate immunity to infection. Further experiments found that blocking the interaction between dendritic cells and T cells during the final stage of Tfh cell formation reduced the production of Tfh cells. Benson et al.'s findings show that the length of time that dendritic cells present antigens on their surface affects the production of Tfh cells and subsequent immune responses. Since Tfh cells are critical to the formation of long-lasting immunity against a virus, these findings could aid efforts to develop more effective vaccines against influenza and other diseases. DOI: http://dx.doi.org/10.7554/eLife.06994.002