Abdulahad W H, van der Geld Y M, Stegeman C A, Kallenberg C G M
Department of Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands.
Kidney Int. 2006 Sep;70(5):938-47. doi: 10.1038/sj.ki.5001670. Epub 2006 Jul 12.
In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell population. Peripheral blood mononuclear cells (PBMCs) were freshly isolated from WG-patients in remission (R-WG, n=40), active WG-patients (A-WG, n=17), and age-matched healthy controls (HCs, n=21). Expression of CD4, CD8, CD45RO, CCR7, interleukin (IL)-18Ralpha, ST2L, and FoxP3 were determined by four-color flow cytometric analysis. CD45RO and CCR7 were used for distinction between naive and memory T cells, IL-18Ralpha, ST2L, and FoxP3 for the assessment of Type1, Type2, and regulatory T-cells, respectively. In R-WG, the CD4+CD45RO+CCR7- effector memory T-cell subpopulation (TEM) was relatively increased, whereas the CD4+CD45RO-CCR7+ naive T-cell population (TNaive) was decreased as compared to HC. The distribution of naive and memory CD8+T cells did not differ between R-WG, A-WG, and HC, nor did CD4+CD45RO+CCR7+ central memory T cells (TCM). In contrast to HC, the percentage of CD4+TNaive cells in R-WG correlated negatively with age, whereas CD4+TEM cells showed a positive correlation. In R-WG, a skewing towards Type2 T cells was observed in CD4+TEM cells. No differences were detected in FoxP3+CD4+TEM cells between R-WG and A-WG, whereas the FoxP3-CD4+TEM cells were increased in R-WG and decreased in A-WG as compared to HC. Collectively, peripheral blood homeostasis of CD4+T cells is disturbed in R-WG with the persistent expansion of non-regulatory CD4+TEM cells. These cells might be involved in relapse and may constitute a target for therapy.
即便处于缓解期,韦格纳肉芽肿病(WG)仍与持续的免疫效应反应相关,我们研究了该病外周血中初始T淋巴细胞和记忆T淋巴细胞的分布情况,并分析了记忆T细胞群体的功能相关表型。从处于缓解期的WG患者(缓解期WG,R-WG,n = 40)、活动期WG患者(活动期WG,A-WG,n = 17)以及年龄匹配的健康对照者(HC,n = 21)中新鲜分离出外周血单个核细胞(PBMC)。通过四色流式细胞术分析测定CD4、CD8、CD45RO、CCR7、白细胞介素(IL)-18Rα、ST2L和FoxP3的表达。CD45RO和CCR7用于区分初始T细胞和记忆T细胞,IL-18Rα、ST2L和FoxP3分别用于评估1型、2型和调节性T细胞。在缓解期WG中,与健康对照相比,CD4 + CD45RO + CCR7 - 效应记忆T细胞亚群(TEM)相对增加,而CD4 + CD45RO - CCR7 + 初始T细胞群体(TNaive)减少。缓解期WG、活动期WG和健康对照之间,初始和记忆CD8 + T细胞的分布以及CD4 + CD45RO + CCR7 + 中央记忆T细胞(TCM)均无差异。与健康对照相反,缓解期WG中CD4 + TNaive细胞的百分比与年龄呈负相关,而CD4 + TEM细胞呈正相关。在缓解期WG中,CD4 + TEM细胞中观察到向2型T细胞的偏移。缓解期WG和活动期WG之间,FoxP3 + CD4 + TEM细胞未检测到差异,而与健康对照相比,缓解期WG中FoxP3 - CD4 + TEM细胞增加,活动期WG中减少。总体而言,缓解期WG中CD4 + T细胞的外周血稳态受到干扰,非调节性CD4 + TEM细胞持续扩增。这些细胞可能参与疾病复发,或许可作为治疗靶点。