Svensson L A, Tarkowski A, Thelestam M, Lagergård T
Department of Medical Microbiology and Immunology, University of Göteborg, Göteborg, S-413 46, Sweden.
Microb Pathog. 2001 Mar;30(3):157-66. doi: 10.1006/mpat.2000.0422.
The Haemophilus ducreyi cytolethal distending toxin (HdCDT) induces cell cycle arrest and thereby inhibits cell proliferation of many cultured mammalian cell-lines. We investigated the effect of HdCDT on circulating human hematopoietic cells, including T- and B-cells, monocytes and polymorphonuclear cells (PMN). Lymphocytes were stimulated with T- and B-cell specific mitogens, whereas monocytes and PMN with endotoxin. HdCDT inhibited the mitogen-induced proliferation of T-cells in a dose-dependent manner as assayed by [(3)H]-thymidine incorporation and MTT assays. Similarly to T-cells, HdCDT also inhibited the proliferation of B-cells and consequently the immunoglobulin production, measured by ELISPOT and ELISA assays. In contrast, the HdCDT did not affect monocytes or PMN, as measured by MTT assay. The TNF-alpha production by monocytes and the phagocytic ability of PMN were neither affected. The monocytic cell line THP-1 was, however, sensitive to the toxin, seen as a reduction of proliferation and viability after exposure to HdCDT. In conclusion, exposure to HdCDT significantly affects the proliferation and other biological activities of stimulated human T- and B-cells, while circulating monocytes and PMN are not sensitive to HdCDT. The sensitivity of cells of the acquired immune system to HdCDT may hamper specific host response to H. ducreyi and contribute to persistence of chancroid lesions.
杜克雷嗜血杆菌细胞致死性膨胀毒素（HdCDT）可诱导细胞周期停滞，从而抑制多种培养的哺乳动物细胞系的细胞增殖。我们研究了HdCDT对循环中的人类造血细胞的影响，这些细胞包括T细胞和B细胞、单核细胞以及多形核细胞（PMN）。用T细胞和B细胞特异性丝裂原刺激淋巴细胞，而用内毒素刺激单核细胞和PMN。通过[³H] - 胸腺嘧啶核苷掺入法和MTT法检测发现，HdCDT以剂量依赖的方式抑制丝裂原诱导的T细胞增殖。与T细胞类似，HdCDT也抑制B细胞的增殖，进而抑制通过ELISPOT和ELISA法检测的免疫球蛋白产生。相比之下，通过MTT法检测发现，HdCDT对单核细胞或PMN没有影响。单核细胞产生的TNF - α以及PMN的吞噬能力均未受影响。然而，单核细胞系THP - 1对该毒素敏感，暴露于HdCDT后可见增殖和活力降低。总之，暴露于HdCDT会显著影响受刺激的人类T细胞和B细胞的增殖及其他生物学活性，而循环中的单核细胞和PMN对HdCDT不敏感。获得性免疫系统细胞对HdCDT的敏感性可能会阻碍宿主对杜克雷嗜血杆菌的特异性反应，并导致软下疳病变持续存在。
