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本研究探讨应用IL-7Rα抗体对Ⅱ型胶原诱导性关节炎(collagen-induced arthritis,CIA)T细胞的作用机制。采用Ⅱ型胶原(collagenⅡ,CⅡ)免疫DBA/1J小鼠建立CIA模型,二次免疫后分别对治疗组和对照组小鼠给予IL-7Rα抗体及其同型对照抗体进行治疗。通过HE染色检测小鼠关节炎性细胞浸润程度;3 H-TdR掺入法检测小鼠脾脏单个核细胞和CD4+T细胞对CⅡ的增殖反应;ELISA检测脾脏单个核细胞培养上清中细胞因子分泌情况;流式细胞术检测小鼠T细胞亚群分布变化情况;real-time PCR检测相关细胞因子及T细胞亚群转录因子mRNA表达水平。实验结果显示:治疗组小鼠关节炎症细胞浸润程度明显减轻;脾脏单个核细胞及CD4+T细胞增殖程度显著降低;脾脏单个核细胞培养上清中的炎性细胞因子IFN-γ、IL-17A、TNF-α含量明显低于对照组;Th1和Th17细胞亚群数量及相应的转录因子mRNA水平明显降低。以上结果提示应用IL-7Rα抗体治疗可能通过抑制致病性T细胞的增殖、减少致病性T细胞数量等途径缓解CIA发病。本研究阐明了IL-7Rα作为拮抗剂治疗CIA的作用机制,并为临床治疗类风湿性关节炎提供了研究基础。
This study was to investigate the mechanism of action of IL-7Rα antibody on collagen-induced arthritis (CIA) T cells. DBA / 1J mice were immunized with collagen Ⅱ (CⅡ) to establish CIA model. After the second immunization, IL-7Rα antibody and its isotype control antibody were given to the treatment group and the control group respectively. The degree of inflammatory cell infiltration was detected by HE staining. The proliferative response of spleen mononuclear cells and CD4 + T cells to CⅡ was detected by 3H-TdR incorporation method. The levels of cytokines in the supernatants of spleen mononuclear cells The changes of distribution of T lymphocyte subsets in mice were detected by flow cytometry. The mRNA expressions of related cytokines and T cell subsets were detected by real-time PCR. The experimental results showed that: the infiltration of inflammatory cells in the treatment group mice significantly reduced; spleen mononuclear cells and CD4 T cell proliferation was significantly reduced; spleen mononuclear cell culture supernatant inflammatory cytokines IFN-γ, IL-17A , TNF-α content was significantly lower than the control group; Th1 and Th17 cell subsets and the corresponding transcription factor mRNA levels were significantly lower. The above results suggest that treatment with IL-7Rα antibody may alleviate the onset of CIA by inhibiting pathogenic T cell proliferation and reducing the number of pathogenic T cells. This study elucidates the mechanism of action of IL-7Rα as an antagonist in the treatment of CIA and provides the basis for the clinical treatment of rheumatoid arthritis.