【摘要】 目的　观察Ⅱ型胶原 (CⅡ ) 2 63 2 72段多肽氨基酸替换对类风湿关节炎 (RA)患者T细胞激活的影响 ,探讨以HLA DRβ1特异性低T细胞反应肽抑制RAT细胞激活的可能性。 方法　分离 3 9例RA患者外周血单个核细胞 (PBMC) ,与去除T细胞受体结合表位的CⅡ修饰肽共同孵育 ,检测T细胞增生情况及患者血清中的CⅡ抗体浓度 ;分析T细胞激活与CⅡ抗体形成以及与患者临床特点的关系。结果　 5 6%的RA患者的T细胞在加入CⅡ 2 63 2 72原型肽和CⅡ蛋白刺激后有明显增生。在T细胞增生阳性的 2 2例RA病人中 ,68%的患者T细胞对替换第 2 68、2 69、2 70位氨基酸的CⅡ 2 63 2 72修饰肽的反应明显低于CⅡ原型肽 (P <0 0 5 )。T细胞增生与CⅡ抗体水平呈显著正相关 (r =0 5 2 9,P <0 0 1)。短病程RA患者的CⅡ特异性T细胞增生较为显著。结论　RA患者的T细胞对去除T细胞受体结合表位的CⅡ修饰肽呈低反应性 ,CⅡ特异性T细胞激活与CⅡ抗体生成有密切关系。低T细胞反应性CⅡ修饰肽可能对类风湿关节炎的T细胞激活有抑制作用更多还原

【Abstract】 Objective To evaluate the effect of CⅡ peptides with substitution for T-cell receptor (TCR) binding residues on T cell activation in rheumatoid arthritis (RA) patients.Methods Peripheral blood mononuclear cells (PBMC) were obtained from 39 RA patients.T cells were cultured with CⅡ protein, wild-typed CⅡ263-272 peptide and modified CⅡ263-272 peptide with consecutive substitution of 268(G),269(P),270(K) by alanine (A) or glycine (G).T cell proliferation was determined by methotetrazolium (MTT) 7 days later.CⅡ antibodies in RA serum were detected by ELISA. Results T cell responses to CⅡ protein and wild-typed CⅡ263-272 peptide were observed in 22 RA patients (56%).The stimulation index (SI) of the modified CⅡ peptide was significantly lower than wild-typed peptide in 15 patients.Activation of CⅡ specific T cell was in correlation with the concentration of CⅡ antibodies.T cell activation in patients with disease duration ≤3 year was significantly higher than in those with longer duration.Conclusion CⅡ specific T cell activation played an important role in early stage of pathogenesis of RA.Non-T cell binding peptide yielded hyporesponse to CⅡ specific T cell activation,suggesting a new strategy of immunosuppresive therapy in RA.更多还原