从健康人外周血建立人软骨抗原凝集原G1区自身反应性T淋巴细胞株

为了研究健康人T细胞库中是否存在G1特异性T细胞 ,我们应用重组人软骨抗原凝集原G1为抗原 (rG1) ,采用国际标准半有限稀释建系法 ,从 4名正常人外周血中建立了 11株rG1特异性T细胞系。 4名健康供者的rG1特异性T细胞系出现频率分别为 0 6 / 10 6(RP )、 0 5 / 10 6(AC )、 1 6 / 10 6(YZ )和 2 0 / 10 6(JY ) ,平均为 1 1± 0 5 / 10 6。远远低于类风湿性关节炎病人外周血rG1特异性自身反应性T细胞。所有T细胞系与rG1及WT和PPD共同培养以观察其特异性反应性 ,结果发现所建立的 11株T细胞系对人软骨抗原凝集素G1区具有良好的特异性。本研究结果提示正常人外周血中确有rG1特异性T细胞系 ,但是出现频率远远低于类风湿性关节炎病人 (另文报道 )。

The Isolation of Autoreactive T Cells Specific to Aggrecan G1 Domain from Healthy Individnnls

Our previous work showed that the cartilage proteoglycan aggrecan can induce an erosive polyarthritis and spondylitis in BALB/c mice and the G1 globular domain of the aggrecan (G1) contains the arthritogenic region Moreover,cellular immunity to G1 is frequently observed in patients with rheumatoid arthritis (RA) However,the G1 reactivity is also found in the peripheral blood of healthy controls in a very low prevalence To see whether autoreactive T cells to G1 are expressed in normal immune repertoire, we analyzed the frequency of human G1 specific T cells in the peripheral blood of four healthy donors and attempted to establish G1 reactive T cell lines from these healthy individuals The results showed that the G1 specific T cells were detectable at the range of 1 1±0 5×10 6 peripheral blood lymphocytes, and 11 G1 specific T lymphocyte lines from these healthy donors were generated with a standard split well method All these cells expressed fine specificity to human recombinant G1,but not to unrelated antigens of WT and PPD Two of them reacted with R16 (G1 residuces 349 374) These data provide strong evidence in favor of the presence of autoreactive T cells in the normal immune repertoire What is the mechanism(s) that these autoreactive T cells do not attack self target in normal conditions and whether these G1 specific T cell lines can induce arthritis in immune deficiency mice are currently under investigation