对病原性抗原的反复暴露会使CD8+T细胞区室重塑,并产生多克隆且复杂的功能记忆库。在克隆型水平,对保守的流感抗原的反应,M158-66在健康个体中具有良好的特征,但不是在接受免疫抑制治疗或免疫异常的患者中,如青少年特发性关节炎(JIA)。在这里,我们显示JIA患者的M158-66特异性RS/RA克隆型数量减少,表明克隆丰富度下降,因此,具有较低的曲目多样性。通过使用秩-频率方法分析曲目的分布,我们发现JIAT细胞库的几个特征类似于健康成人中看到的库,包括扩增的RS/RA特异性抗原反应,代表更大的克隆不均匀性。与成熟的曲目不同,然而,克隆型分布波动更大,克隆型稳定性较低,JIA中M158-66特异性RS/RA克隆型的IFNy反应更多。这表明在免疫抑制疗法中JIA患者的功能克隆扩增发生了改变。我们建议对这里描述的流感M158-66表位的反应是接受免疫抑制治疗的JIA患者的普遍现象。克隆丰富度和不均匀性的变化表明成熟免疫反应的产生迟缓和不均匀。
Recurrent exposures to a pathogenic antigen remodel the CD8+ T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M158-66 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M158-66 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M158-66 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M158-66 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.