Biomedical Sciences Dept, Defence Science and Technology laboratory (DSTL) Porton Down, Salisbury, United Kingdom.
PLoS One. 2013 Sep 30;8(9):e74789. doi: 10.1371/journal.pone.0074789. eCollection 2013.
Burkholderia pseudomallei is a dangerous human pathogen. Phosphoantigens specifically the target primate specific γ9(+)δ2(+) T cells subset and some have been developed as potential immunotherapeutics. Previously, we demonstrated that, when stimulated with the phosphoantigen CHDMAPP, γ9(+)δ2(+) T cells aid in the killing of intracellular B. pseudomallei bacteria. Moreover, we found that common marmoset (Callithrix Jacchus) γ9(+) T cells increase in frequency and respond to the phosphoantigen CHDMAPP and/or B. pseudomallei, in combination with IL-2, in a similar manner to human γ9(+)δ2(+) T cells. Here we evaluate the efficacy of the phosphoantigen CHDMAPP, in combination with IL-2, as a therapy against B. pseudomallei infection, in vivo. We found that the previous studies predicted the in vivo responsiveness of γ9(+) T cells to the CHDMAPP+IL-2 treatment and significant expansion of the numbers of peripheral and splenic γ9(+) T cells were observed. This effect was similar to those reported in other primate species treated with phosphoantigen. Furthermore, splenocytes were retrieved 7 days post onset of treatment, restimulated with CHDMAPP or heat-killed B. pseudomallei and the cultured γ9(+) T cells demonstrated no reduction in IFN-γ response when CHDMAPP+IL-2 animals were compared to IL-2 only treated animals. Using an established model of B. pseudomallei infection in the marmoset, we assessed the potential for using phosphoantigen as a novel immunotherapy. The CHDMAPP treatment regime had no effect on the progression of respiratory melioidosis and this was despite the presence of elevated numbers of γ9(+) T cells in the spleen, liver and lung and an increased proportion of IFN-γ(+) cells in response to infection. We therefore report that the common marmoset has proven a good model for studying the effect in vivo of γ9(+) T cell stimulation; however, γ9(+) T cells have little or no effect on the progression of lethal, respiratory B. pseudomallei infection.
类鼻疽伯克霍尔德菌是一种危险的人类病原体。磷酸抗原，特别是靶向灵长类动物特异性γ9(+)δ2(+)T 细胞亚群的磷酸抗原，已被开发为潜在的免疫治疗药物。此前，我们证明了当受到磷酸抗原 CHDMAPP 的刺激时，γ9(+)δ2(+)T 细胞有助于杀死细胞内的类鼻疽伯克霍尔德菌细菌。此外，我们发现普通狨猴（Callithrix Jacchus）γ9(+)T 细胞的频率增加，并以类似于人类 γ9(+)δ2(+)T 细胞的方式对磷酸抗原 CHDMAPP 和/或类鼻疽伯克霍尔德菌作出反应，同时还对 IL-2 作出反应。在这里，我们评估了磷酸抗原 CHDMAPP 与 IL-2 联合作为治疗类鼻疽伯克霍尔德菌感染的方法的疗效，进行了体内研究。我们发现，之前的研究预测了 γ9(+)T 细胞对 CHDMAPP+IL-2 治疗的体内反应性，并且观察到外周血和脾脏 γ9(+)T 细胞数量显著增加。这种效应类似于其他用磷酸抗原治疗的灵长类动物所报道的效应。此外，在治疗开始后 7 天回收脾细胞，用 CHDMAPP 或热灭活的类鼻疽伯克霍尔德菌再刺激，与仅用 IL-2 治疗的动物相比，用 CHDMAPP+IL-2 治疗的动物的 γ9(+)T 细胞的 IFN-γ 反应没有减少。我们在狨猴中建立了类鼻疽伯克霍尔德菌感染的模型，评估了磷酸抗原作为新型免疫疗法的潜力。CHDMAPP 治疗方案对呼吸道类鼻疽病的进展没有影响，尽管脾脏、肝脏和肺部的 γ9(+)T 细胞数量增加，对感染的 IFN-γ(+)细胞比例增加。因此，我们报告说，普通狨猴已被证明是研究体内 γ9(+)T 细胞刺激效应的良好模型；然而，γ9(+)T 细胞对致命性呼吸道类鼻疽伯克霍尔德菌感染的进展几乎没有影响。
