类风湿关节炎T细胞亚群4—1BB的表达与其分泌TH1／TH2细胞因子的关系

Expression of 4-1BB on T lymphocytes and relationship with TH 1/TH2 cytokines from patients with rheummatoid arthritis

目的探讨体外培养的类风湿关节炎（rheumatoid arthritis，RA）T淋巴细胞上共刺激分子4-1BB的表达，及与其分泌TH1，TH2细胞因子的关系。方法应用流式细胞术检测体外培养的30例RA患者和20例正常对照者T细胞活化前后4-1BB的表达，并且应用ELISA方法检测培养上清液中IFN-γ、IL-4水平。结果RA患者CD^4＋T和CD^8＋T细胞表达的4-1BB明显高于正常对照组（表达百分率分别为18．56％±4．08％和10．33％±2．13％；1．24％±0．12％和0．87％±0．09％，P〈0．01），经抗CD3单抗体外刺激后CD4^＋T和CD8^＋T细胞表达的4-1BB均显著高于活化前（表达百分率为33．21％±4．29％和21．35％±8．12％，P〈0．01）。RA患者CD4^＋T／CD8^＋T比值明显升高，而且与4-1BB^＋CD4^＋T细胞数呈正相关关系（r=0．84，P〈0．01），RA患者T淋巴细胞培养液上清中IFN-γ、IL-4均高于正常对照组（P〈0．05），经抗CD3单抗体外刺激后上清液中IFN-γ及IL-4均明显高于活化前，以IFN-γ升高最为显著（P〈0．01）。而且抗CD3单抗刺激前后4-1BB^＋CD4^＋T细胞数与培养上清液中IFN-γ水平均呈正相关关系（r=0．721，r=0．487，P〈0．05）。结论类风湿关节炎患者T细胞表达的4-1BB在类风湿关节炎的发生发展中具有重要意义，4-1BB可能通过对CD4^＋T细胞活化，促使TH1细胞因子分泌，参与关节炎症和免疫损伤。

Objective To investigate the expression of costimulatory molecule 4-1BB on T cell of patients with rheumatoid arthritis （RA） and the relationship with the levels of IFN-γ,IL-4 in culture supernatant of T ceil. Methods The expression of 4-1BB on T lymphocyte from 30 RA patients and 20 healthy controls were assayed by Flow cytometry. The level of IFN-γ and IL-4 in supernatant were measured by ELISA. Results The expression of 4-1BB on CD4^＋ T and CD8^＋ T lymphocytes from RA patients were significantly higher than that from normal control（18.56% ±4.08%,10.33% ±2.13% vs 1.24% ±0.12%, 0.87% ±0.09%, P〈0.01）. After anti-CD3 stimulation, the expression of 4-1BB on CD4^＋ T and CD8^＋ T lymphocytes from RA patients was significantly increased （33.21% ± 4.2%, 21.35 % ± 8.12%, P 〈 0.01 ）. In addition, the ratio of CD4^＋ T/CD8^＋ T in RA patients was higher than that in normal control and positively correlated with the count of 4-1BB^＋ CD4^＋ T cell. The levels of IFN-γ and IL-4 in RA patient were distinguished higher than that of control, and the contents of IFN-γ and IL-4 in supernatant of RA patients were significantly increased after anti-CD3 stimulation. The expression of 4-1BB on CD4^＋ T in RA patients was positively correlated with the levels of IFN-γ in supernatant before and after anti-CD3 stimulation （ r = 0.721, r = 0.487, P 〈 0.05）. Conclusion The costimulatory molecule 4- 1BB is abnormally expressed in T lymphocytes from patients with rheumatoid arthritis. The abnormal expression of 4-1BB on T lymphocytes may play an important role in the development of RA. The expression of 4-1BB on CD4^＋ T cell may take part in immune inflammation of RA by activating CD4 ^＋ T cell and increasing TH1 cytokines.