CD52单抗通过清除活化T细胞对IL-10基因敲除小鼠结肠炎的干预作用

Anti-mouse CD52 monoclonal antibody treatment inhibits colitis in IL-10 deficient mice by the depletion of activated T cells

目的:观察CD52单抗对IL-10基因敲除小鼠结肠炎的干预作用并探究其干预作用的可能机制。方法:给予CD52单抗治疗后,计算疾病活动度指数,检测结肠病理学评分,外周血、脾脏及结肠固有层单个核细胞中T淋巴细胞的清除情况,结肠组织炎性因子水平及相关细胞因子的m RNA转录水平的变化。结果:CD52单抗能有效降低疾病活动度评分、结肠病理学评分,能显著地清除模型小鼠外周血、脾脏及结肠固有层单个核细胞中CD3+T细胞,明显降低结肠组织中IFN-γ、IL-17的表达水平,同时增加了IL-5和IL-13的表达,并相应下调TNF-α、IFN-γ、IL-17和IL-6及炎症调控因子IL-12和IL-23的m RNA表达水平。结论:抗CD52单抗能有效地治疗IL-10基因敲除小鼠的结肠炎,其干预效果与活化T细胞的直接清除相关,此外,其对IL-12/23通路的下调及Th2反应的诱导作用亦可能与干预作用相关。

Objective： To investigate the therapeutic effects and potential mechanisms of anti-CD52 treatment in IL-10 deficient mice with colitis. Methods： After anti-CD52 treatment, disease activity index and the histological grading of colitis were quantified, depletion of CD3＋ T cells among peripheral blood, spleen and colon lamina propria mononuclear cells were analyzed by FACS, the IFN-γ and IL-17 levels were tested by ELISA and the m RNA transcriptional levels of T-cell related cytokines were also tested. Results： The disease activity index and histological grading were significantly decreased by anti-CD52 treatment. The percentage of CD3＋ T cells in blood, spleen and colon lamina propria mononuclear cells were decreased respectively. The treatment decreased the levels of IFN-γ and IL-17 and increased the expression of IL-5 and IL-13 in colon tissues significantly. The m RNA expressions of TNF-α, IFN-γ, IL-17, IL-6 and related regulating factor IL-12 and IL-23 were also down-regulated. Conclusions： Anti-CD52 treatment inhibits the colitis of IL-10 deficient mice and it may be related to the depletion of activated T cells. Besides,the downregulation of IL-12/23 inflammatory pathway and the induction of Th2 response may also play a role in the process.