Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses.
Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses.
复制标题
DOI：
10.4049/jimmunol.1000999
复制
发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Oh S
中科院分区：
文献类型：
--
作者：
Ni L;Gayet I;Zurawski S;Duluc D;Flamar AL;Li XH;O'Bar A;Clayton S;Palucka AK;Zurawski G;Banchereau J;Oh S
Dectin-1是一种识别真菌和分枝杆菌病原体的C型凝集素，可以传递激活树突状细胞（DC）的细胞内信号，导致免疫应答的启动和Th 17 CD 4 + T细胞应答的扩增。在这里，我们研究了在DC上表达的人Dectin-1（hDectin-1）在抗原特异性CD 8 + T细胞应答的诱导和激活中的作用。我们首先产生了激动性抗hDectin-1单克隆抗体（mAb），其识别hDectin-1 Glu 143-Ile 162区域。它结合在体外单核细胞来源的DC和在体内的CD 1c + CD 1a+真皮DC，但不表皮朗格汉斯细胞。抗hDectin-1介导的DC活化导致共刺激分子的上调以及多种细胞因子和趋化因子以Syk依赖性方式的分泌。抗hDectin-1单克隆抗体激活的DC可通过促进CD 8 + T细胞的扩增及其功能活性而显著增强neo和外源抗原特异性CD 8 + T细胞应答。我们进一步证明了使用抗hDectin-1-抗原缀合物经由hDectin-1将抗原递送至DC导致有效的抗原特异性CD 8 + T细胞应答。因此，在DC上表达的hDectin-1可以有助于诱导和激活针对细胞内病原体（例如分枝杆菌）的细胞免疫，所述细胞内病原体通过Dectin-1被DC识别。基于用激动性抗hDectin-1 mAb将抗原递送至DC的疫苗可以引发CD 8 + T细胞介导的免疫。
Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4+ T cell responses. Here, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of antigen-specific CD8+ T cell responses. We first generated an agonistic anti-hDectin-1 monoclonal antibody (mAb), which recognizes the hDectin-1 Glu143-Ile162 region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c+CD1a+ dermal DCs, but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign antigen-specific CD8+ T cell responses by promoting both the expansion of CD8+ T cell and their functional activities. We further demonstrated that delivering antigens to DCs via hDectin-1 using anti-hDectin-1-antigen conjugates resulted in potent antigen-specific CD8+ T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering antigens to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8+ T cell-mediated immunity.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
影响因子：
4.4
作者：
Carter, Robert W.;Thompson, Clare;Tough, David F.
通讯作者：
Tough, David F.