Regulation of Acquired Immunity by γδ T‐Cell/Dendritic‐Cell Interactions
Regulation of Acquired Immunity by γδ T‐Cell/Dendritic‐Cell Interactions
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γδ T 细胞/树突状细胞相互作用调节获得性免疫
DOI：
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
P. Haslett
中科院分区：
文献类型：
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作者：
N. Shrestha;J. Ida;A. Lubiński;Maria F. Pallin;G. Kaplan;P. Haslett
摘要：在人类中，分枝杆菌（包括结核分枝杆菌和麻风分枝杆菌）的先天免疫识别涉及在未成熟树突状细胞（DC）上表达的Toll样受体-2（TLR-2）和由利用Vδ2的T细胞亚群（Vδ2 T细胞）表达的T细胞γδ受体。为了研究这些宿主细胞群在微生物环境中的调节关系，分别用模型TLR-2配体和磷酸化抗原刺激的人DC和Vδ2 T细胞进行体外实验。我们观察到TLR-2刺激的DC增强Vδ2 T细胞产生干扰素-γ（IFN-γ）;相反，活化的Vδ2 T细胞通过包括IFN-γ在内的可溶性因子增强TLR-2诱导的DC成熟，其共刺激DC分泌白细胞介素-12（IL-12）p70。当TLR-2刺激有限时，DC暴露于活化的Vδ2 T细胞对于Th 1 T-细胞引发至关重要。这些结果表明，当缺乏TLR-2刺激时，Vδ2 T细胞可能在引发保护性抗分枝杆菌免疫中发挥佐剂作用，如果感染性接种物很小，或者如果病原体是DC的内在弱激活剂，则可能发生这种情况。
Abstract: In humans, innate immune recognition of mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae, involves toll‐like receptor‐2 (TLR‐2), expressed on immature dendritic cells (DCs), and the T‐cell γδ receptor expressed by a subpopulation of T cells that utilize Vδ2 (Vδ2 T cells). To investigate modulatory relationships between these host‐cell populations in a microbial context, in vitro experiments were performed with human DCs and Vδ2 T cells stimulated with model TLR‐2 ligands and phosphoantigens, respectively. We observed that TLR‐2‐stimulated DCs enhanced interferon‐γ (IFN‐γ) production by Vδ2 T cells; conversely, activated Vδ2 T cells enhanced TLR‐2‐induced DC maturation via soluble factors including IFN‐γ, which costimulated interleukin‐12 (IL‐12) p70 secretion by DCs. Exposure of DCs to activated Vδ2 T cells was critical for Th1 T‐cell priming when TLR‐2 stimulation was limiting. These results suggest that Vδ2 T cells may play an adjuvant role in priming protective antimycobacterial immunity when TLR‐2 stimulation is lacking, as may occur if the infectious inoculum is small, or if the pathogen is an intrinsically weak activator of DCs.