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目的探讨新型苯并噻唑衍生物BD759抑制T细胞增殖的作用机制。方法流式细胞术检测T细胞增殖、CD25表达及细胞周期。酶联免疫吸附法测定BD759对活化T细胞分泌白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-10、白细胞介素-17A及干扰素-γ等细胞因子的影响。结果 BD759抑制抗人CD3和CD28m Abs刺激的T细胞增和混合淋巴细胞反应,IC50分别为(3.5±0.7)和(3.3±0.9)μmol·L-1。BD759对人静息T细胞和外周血单个核细胞无细胞毒性。BD759不抑制活化的T细胞表达CD25和分泌细胞因子白细胞介素-2、白细胞介素-4及白细胞介素-10,但显著抑制白细胞介素-6、白细胞介素-17A和干扰素-γ的产生,并且阻滞细胞周期于G0/G1期。结论新型苯并噻唑衍生物BD759不影响T细胞的活化,但通过阻滞细胞周期于G0/G1期抑制活化的T细胞增殖,并抑制白细胞介素-6、白细胞介素-17A和干扰素-γ等促炎细胞因子的分泌。BD759有望作为先导化合物,开发用于自身免疫性疾病与器官移植的新型药物。
Aim To investigate the mechanism of BD759, a novel benzothiazole derivative, on the proliferation of T cells. Methods Flow cytometry was used to detect T cell proliferation, CD25 expression and cell cycle. The effect of BD759 on the secretion of IL-2, IL-4, IL-6, IL-10, IL-17A and IFN- influences. Results BD759 inhibited T cell proliferation and mixed lymphocyte responses stimulated by anti-human CD3 and CD28m Abs with IC50 of (3.5 ± 0.7) and (3.3 ± 0.9) μmol·L-1, respectively. BD759 is cytotoxic to human resting T cells and peripheral blood mononuclear cells. BD759 does not inhibit activated T cells expressing CD25 and secreting cytokines interleukin-2, interleukin-4 and interleukin-10, but significantly inhibits interleukin-6, interleukin-17A and interferon-gamma And arrested cell cycle at G0 / G1 phase. Conclusion The new benzothiazole derivative BD759 does not affect the activation of T cells but inhibits the proliferation of activated T cells and blocks the effects of interleukin - 6, interleukin - 17A and interferon - γ and other pro-inflammatory cytokines secretion. BD759 is expected as a lead compound for the development of new drugs for autoimmune diseases and organ transplantation.