St George's University of London, London, UK.
Immunol Cell Biol. 2013 Aug;91(7):461-8. doi: 10.1038/icb.2013.30. Epub 2013 Jun 25.
γδ T cells contribute to immunosurveillance of pathogenic infections and malignant transformations; however, mechanisms of activation have yet to be fully defined. In this study we demonstrate a novel mechanism by which human Vδ2(+) γδ T cells are activated by the model pathogen Bacillus Calmette Guérin (BCG). We show in vitro that Vδ2 cell cytokine production and cytotoxic activity in response to BCG are dependent on both dendritic cells (DCs) and memory CD4(+) αβ T cells (CD4 T cells). We found that Vδ2 cells are indirectly activated by BCG in an interleukin (IL)-12p70-dependent manner, and that DC production of the IL-12p70 responsible for Vδ2 cell activation requires Toll-like receptor 2/4 ligands from BCG and interferon (IFN)-γ from memory CD4 T cells. Our data suggest that Vδ2 cell responses to BCG are dependent on the activation of IFN-γ-producing memory CD4 T cells, and provide novel insight into the complex interplay between cells of the innate and adaptive immune response.
γδ T 细胞有助于对病原感染和恶性转化的免疫监视；然而，其激活机制尚未完全确定。在这项研究中，我们证明了一种新型机制，即模型病原体卡介苗（BCG）可激活人 Vδ2(+)γδ T 细胞。我们在体外表明，Vδ2 细胞对 BCG 的细胞因子产生和细胞毒性活性依赖于树突状细胞（DC）和记忆 CD4(+)αβ T 细胞（CD4 T 细胞）。我们发现，Vδ2 细胞通过 BCG 以白细胞介素（IL）-12p70 依赖的方式间接激活，而负责 Vδ2 细胞激活的 DC 产生的 IL-12p70 需要来自 BCG 的 Toll 样受体 2/4 配体和记忆 CD4 T 细胞中的干扰素（IFN）-γ。我们的数据表明，Vδ2 细胞对 BCG 的反应依赖于 IFN-γ产生的记忆 CD4 T 细胞的激活，为先天和适应性免疫反应细胞之间的复杂相互作用提供了新的见解。
