类风湿关节炎患者外周血T细胞抑制性多肽的研究  

The study of inhibitory peptides on T cell activation in rheumatoid arthritis

作　　者：李霞[1] 李茹 张翠华[1] 栗占国[1] 

机构地区：[1]北京大学人民医院风湿免疫科,100044

出　　处：《中华医学杂志》2005年第24期1679-1682,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30271223);国家杰出青年基金资助项目(30025040)

摘　　要：目的探讨HLADRB1结合性流感病毒血凝素(HA)308317变构肽对类风湿关节炎(RA)患者外周血T细胞激活的影响。方法选取27例HLADRB1阳性的RA患者,密度梯度离心法分离外周血单个核细胞。采用固相法合成HA308317变构肽,并检测RA患者外周血T细胞对这些多肽的反应性;及多肽对白细胞介素(IL)2、γ干扰素分泌及CD69表达的影响。同时进一步观察HA308317变构肽对CII263272或HA308317多肽介导的T细胞激活的抑制作用。结果变构肽刺激T细胞增殖的阳性率分别为7.4%(APL1)、3.7%(APL2)和3.7%(APL3),明显低于CII263272和HA308317原型肰(62.2%和52.9%),3条变构肽的刺激指数也明显低于原型肽(均P<0.01)。并且,其诱导IL2、γ干扰素分泌的水平及CD69的表达亦下降(P<0.05)。与单独加入CII263272或HA308317原型肽的对照组相比,加入HA308317变构肽的T细胞增殖的刺激指数明显下降(P<0.05)。结论替换HA308317多肽中T细胞受体的接触残基产生了弱或非T细胞刺激肽,它们可能有效地抑制RA的T细胞免疫反应。Objective To study the inhibitory role of altered HA308-317 peptides in T cell responses in patients with rheumatoid arthritis (RA). Methods Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DRB1 positive RA patients. T cell responses to altered HA308-317 peptides were examined by using 3H incorporation assay. The level of IL-2 and IFNγ in the supernatants was identified by an enzyme-linked immunosorbent assay. The CD69 expression on T cell surface was studied by using flow cytometry. Results Compared to wild type CII263-272 or HA308-317, altered HA 308-317 peptides failed to stimulate T cell proliferation(P<0.05) and production of IL-2 as well as IFNγ and resulted in lower expression of CD69 in RA patients(P<0.05). SI values for T cell coincubated with altered HA308-317 peptides and CII263-272 or wild type HA308-317 were significantly lower than coincubated with CII263-272 and wild type HA308-317 alone (P<0.05). Conclusion Substitution of TCR-binding residue of HA308-317 yielded weak or non-T-cell stimulating peptides, which might be potentially effective in blocking abnormal T cell responses in RA.

关 键 词：外周血T细胞 关节炎患者 多肽 HLA-DRB1 抑制性 外周血单个核细胞 流感病毒血凝素 密度梯度离心法 T细胞激活 T细胞增殖 类风湿关节炎 细胞免疫反应 RA患者 CD69 γ干扰素 刺激指数 变构肽 白细胞介素 T细胞受体 抑制作用 

分 类 号：R593.22[医药卫生—内科学]