Perticarari Sandra, Presani Gianni, Prodan Mario, Granzotto Marilena, Murgia Rossella, Cinco Marina
Laboratorio di Immunologia, IRCCS Burlo Garofolo, Via Dell'Istria 65/1, Trieste 34147, Italy.
Microb Pathog. 2003 Oct;35(4):139-45. doi: 10.1016/s0882-4010(03)00096-2.
Borrelia burgdorferi is the causative agent of Lyme disease. We investigated whether the in vitro co-cultivation of lymphocytes with spirochetes would induce apoptosis in human lymphocytes. Peripheral blood mononuclear cell were mixed with various ratio of cell/spirochetes (1:10, 1:20, 1:50, 1:100) and incubated in a humified atmosphere of 5% CO(2) at 37 degrees C. Apoptosis was determined at 0, 4, 24 h by Annexin V binding assay and propidium iodide staining, and by CD95 Apo-1 expression. Analysis was performed by multiparametric flow cytometry on CD3, CD4, CD8, CD19 subset of lymphocytes. The binding of Annexin V increased at 24 h in T lymphocytes infected by living spirochetes at ratio 1:50; similar results were obtained with inactivated or sonicated spirochetes and lipidated OspC. The rate of Annexin V binding and pattern of CD95 over-expression were different in CD3, CD4, CD8 and CD19 subset; interleukine-10 (IL-10) was measured in supernatants of cultures after treatment with Borrelia preparations and with OspA and OspC, lipidated or not. Our data suggest that spirochetes were able to induce apoptosis on lymphocytes; the phenomenon appears associated with number of spirochetes, incubation time and the release of IL-10 in co-cultures. Moreover apoptosis was probably Fas-mediated and the cells involved were prevalently CD4.
伯氏疏螺旋体是莱姆病的病原体。我们研究了淋巴细胞与螺旋体的体外共培养是否会诱导人淋巴细胞凋亡。将外周血单核细胞与不同比例的细胞/螺旋体(1:10、1:20、1:50、1:100)混合,并在37℃、5%二氧化碳的湿润气氛中孵育。在0、4、24小时通过膜联蛋白V结合试验、碘化丙啶染色以及CD95 Apo-1表达来测定凋亡情况。通过多参数流式细胞术对淋巴细胞的CD3、CD4、CD8、CD19亚群进行分析。在24小时时,与活螺旋体以1:50比例感染的T淋巴细胞中,膜联蛋白V的结合增加;用灭活或超声处理的螺旋体以及脂化的OspC也得到了类似结果。膜联蛋白V的结合率和CD95过表达模式在CD3、CD4、CD8和CD19亚群中有所不同;在用伯氏疏螺旋体制剂以及脂化或未脂化的OspA和OspC处理后的培养上清液中检测白细胞介素-10(IL-10)。我们的数据表明螺旋体能够诱导淋巴细胞凋亡;该现象似乎与螺旋体数量、孵育时间以及共培养中IL-10的释放有关。此外,凋亡可能是由Fas介导的,且涉及的细胞主要是CD4细胞。