Thewissen Marielle, Somers Veerle, Venken Koen, Linsen Loes, van Paassen Pieter, Geusens Piet, Damoiseaux Jan, Stinissen Piet
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Agoralaan, Diepenbeek, Belgium, and Department of Clinical and Experimental Immunology, University Hospital Maastricht, The Netherlands.
Clin Immunol. 2007 May;123(2):209-18. doi: 10.1016/j.clim.2007.01.005. Epub 2007 Feb 21.
The objective of this study was to evaluate the degree of immunosenescence in patients with autoimmune disease. T cell receptor excision circles (TREC) and the percentage of CD4+CD28null T cells were studied as markers of immunosenescence in 175 patients with chronic autoimmune arthritis, other connective tissue autoimmune diseases, multiple sclerosis and 60 healthy controls. In both the rheumatoid arthritis (RA) and multiple sclerosis patient group, TREC numbers were age-inappropriately declined which points to an accelerated thymic output. Furthermore, enhanced percentages of CD4+CD28null T cells could be detected in a significant proportion of patients included in this study. These immunosenescent phenomena seemed to be present already early in the disease process. High percentages of CD4+CD28null T cells were associated with the presence of RA linked HLA DR4 alleles and with plasma reactivity to cytomegalovirus. Further analysis of CD4+CD28null T cells provided indications for a restricted T cell receptor (TCR) BV gene expression and cytoplasmic stores of various cytotoxic molecules. This study indicates that the immune system of patients with autoimmune diseases shows signs of an accelerated aging. Both genetic factors, such as HLA DR4, and environmental factors, like CMV infection, might speed up this immunosenescence and contribute in this way to disease pathogenesis.
本研究的目的是评估自身免疫性疾病患者的免疫衰老程度。研究了175例慢性自身免疫性关节炎、其他结缔组织自身免疫性疾病、多发性硬化症患者以及60名健康对照者的T细胞受体切除环（TREC）和CD4 + CD28阴性T细胞百分比，以此作为免疫衰老的标志物。在类风湿性关节炎（RA）和多发性硬化症患者组中，TREC数量均出现与年龄不符的下降，这表明胸腺输出加速。此外，在本研究纳入的相当一部分患者中可检测到CD4 + CD28阴性T细胞百分比增加。这些免疫衰老现象似乎在疾病进程早期就已出现。高百分比的CD4 + CD28阴性T细胞与RA相关的HLA DR4等位基因的存在以及对巨细胞病毒的血浆反应性有关。对CD4 + CD28阴性T细胞的进一步分析显示，其T细胞受体（TCR）BV基因表达受限，且存在各种细胞毒性分子的细胞质储存。本研究表明，自身免疫性疾病患者的免疫系统显示出加速衰老的迹象。遗传因素，如HLA DR4，以及环境因素，如巨细胞病毒感染，可能会加速这种免疫衰老，并以此方式促进疾病发病机制。
