Mbow M L, Zeidner N, Panella N, Titus R G, Piesman J
Division of Vector-Borne Infectious Diseases, National Center for Infectious Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522, USA.
Infect Immun. 1997 Aug;65(8):3386-90. doi: 10.1128/iai.65.8.3386-3390.1997.
Borrelia burgdorferi-pulsed dendritic cells and epidermal cells were able to initiate the production of anti-outer surface protein A (OspA) antibody in vitro with normal T and B cells from either BALB/c or C3H/HeJ mice. Inhibition of anti-B. burgdorferi antibody production was observed after 3 days, but not after 2 days, of exposure of the antigen-presenting cells to tumor necrosis factor alpha +/- granulocyte-macrophage colony-stimulating factor. Furthermore, splenic dendritic cells pulsed in vitro with live B. burgdorferi spirochetes and then adoptively transferred into naive syngeneic mice mediated a protective immune response against tick-transmitted spirochetes. This protection appeared not to be due to killing of spirochetes in the feeding ticks, since ticks fed to repletion on B. burgdorferi-pulsed dendritic cell-sensitized mice still harbored live spirochetes. Western blot analysis of the sera collected from dendritic cell-sensitized mice demonstrated that the mice responded to a limited set of B. burgdorferi antigens, including OspA, -B, and -C compared to control groups that either had received unpulsed dendritic cells or were not treated. Finally, mice in the early stage of B. burgdorferi infection were able to develop anti-OspA antibody following injection with B. burgdorferi-pulsed dendritic cells. Our results demonstrate for the first time that adoptive transfer of B. burgdorferi-pulsed dendritic cells induces a protective immune response against tick-transmitted B. burgdorferi and stimulates the production of antibodies specific for a limited set of B. burgdorferi antigens in vivo.
伯氏疏螺旋体脉冲树突状细胞和表皮细胞能够在体外与来自BALB/c或C3H/HeJ小鼠的正常T细胞和B细胞一起启动抗外表面蛋白A(OspA)抗体的产生。在抗原呈递细胞暴露于肿瘤坏死因子α+/-粒细胞巨噬细胞集落刺激因子3天后观察到抗伯氏疏螺旋体抗体产生受到抑制,但2天后未观察到抑制。此外,体外用人活伯氏疏螺旋体脉冲的脾树突状细胞,然后过继转移到同基因的未致敏小鼠中,介导了针对蜱传播螺旋体的保护性免疫反应。这种保护似乎不是由于在取食蜱中杀死螺旋体,因为在伯氏疏螺旋体脉冲树突状细胞致敏小鼠身上饱食的蜱仍携带着活的螺旋体。对从树突状细胞致敏小鼠收集的血清进行的蛋白质印迹分析表明,与接受未脉冲树突状细胞或未处理的对照组相比,这些小鼠对一组有限的伯氏疏螺旋体抗原作出反应,包括OspA、-B和-C。最后,处于伯氏疏螺旋体感染早期的小鼠在注射伯氏疏螺旋体脉冲树突状细胞后能够产生抗OspA抗体。我们的结果首次证明,过继转移伯氏疏螺旋体脉冲树突状细胞可诱导针对蜱传播的伯氏疏螺旋体的保护性免疫反应,并在体内刺激产生针对一组有限的伯氏疏螺旋体抗原的特异性抗体。