Kingston R, Burke F, Robinson J H, Bedford P A, Jones S M, Knight S C, Williamson E D
Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, Watford Road, Harrow, UK.
Clin Exp Immunol. 2007 Sep;149(3):561-9. doi: 10.1111/j.1365-2249.2007.03452.x. Epub 2007 Jul 23.
The F1 and V antigens of Yersinia pestis, despite acting as virulence factors secreted by the organism during infection, also combine to produce an effective recombinant vaccine against plague, currently in clinical trial. The protective mechanisms induced by rF1 + rV probably involve interactions with dendritic cells (DC) as antigen uptake, processing and presenting cells. To study such interactions, naive ex vivo DC from bone marrow, spleen and lymph node were cultured with rF1, rV or combined antigens and demonstrated to secrete interleukin (IL)-4 and IL-12 into the culture supernatant. Cytokine production in response to pulsing was dependent on the maturity of the bone marrow-derived DC culture, so that pulsed 8-day-old cultures had accumulated significantly more intracellular IL-4 and IL-12 than unpulsed cells. DC, pulsed with rF1 + rV for 2-24 h, were able to prime naive autologous lymph node T cells to proliferate in an antigen dose-dependent manner, with an order of potency of 3d bone marrow-derived DC (BMDC) > 7d BMDC > splenic DC. Significantly, cell-free supernatants from rF1 + rV-pulsed BMDC and splenic DC were also able to induce specific primary responses effectively in naive T cells, suggesting that these supernatants contained stimulatory factor(s). This study suggests an important role for DC, or factors secreted by them, in the induction of protective immunity to plague by the rF1 and rV antigens.
鼠疫耶尔森菌的F1和V抗原，尽管在感染过程中作为该菌分泌的毒力因子起作用，但二者结合可产生一种有效的抗鼠疫重组疫苗，目前正处于临床试验阶段。rF1 + rV诱导的保护机制可能涉及与作为抗原摄取、加工和呈递细胞的树突状细胞（DC）相互作用。为研究此类相互作用，将来自骨髓、脾脏和淋巴结的未经刺激的体外DC与rF1、rV或联合抗原一起培养，并证明其可将白细胞介素（IL）-4和IL-12分泌到培养上清液中。对脉冲刺激产生的细胞因子分泌取决于骨髓来源的DC培养物的成熟度，因此，经脉冲刺激的8日龄培养物比未刺激的细胞积累了显著更多的细胞内IL-4和IL-12。用rF1 + rV脉冲刺激2至24小时的DC能够使未经刺激的自体淋巴结T细胞以抗原剂量依赖性方式增殖，其效力顺序为3日龄骨髓来源的DC（BMDC）> 7日龄BMDC>脾DC。值得注意的是，来自rF1 + rV脉冲刺激的BMDC和脾DC的无细胞上清液也能够在未经刺激的T细胞中有效诱导特异性初级反应，这表明这些上清液含有刺激因子。本研究表明DC或其分泌的因子 在rF1和rV抗原诱导的鼠疫保护性免疫中起重要作用。
