Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome
Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome
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DOI：
10.1111/j.1365-2249.2006.03038.x
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发表时间：
2006-04-01
影响因子：
4.6
通讯作者：
Hara, T
中科院分区：
文献类型：
--
作者：
Kanaya, Y;Ohga, S;Hara, T
染色体22q11.2缺失综合征是一种以胸腺发育不全、心脏圆锥干缺损和甲状旁腺功能低下为特征的常见疾病。患者有感染和自身免疫的风险，与T淋巴细胞减少症相关。为了评估患者的免疫结构，通过流式细胞术和实时聚合酶链反应（PCR）分析循环T细胞的数量变化和细胞因子谱。从出生到成年，患者组的CD 3（+）、CD 4（+）、T细胞受体（TCR）α β（+）或CD 8 α α（+）细胞计数低于对照组，而CD 56（+）细胞计数高于对照组。CD 3（+）、CD 4（+）细胞数的衰老性下降较对照组慢。对照组中CD 8 α α（+）细胞的比例增加，斜率指数大于患者。另一方面，V α 24（+）细胞的数量和比例在患者中均增加，并且斜率指数倾向于大于对照组。仅在患者中观察到T细胞数量与CD 8 α α（+）细胞的正相关，仅在对照组中观察到与V α 24（+）细胞的正相关。在患者和对照组之间，T细胞中干扰素（IFN）-γ、白细胞介素（IL）-10、转化生长因子（TGF）-β、细胞毒性T淋巴细胞抗原4（CTLA 4）或叉头框p3（Foxp 3）的基因表达水平没有差异。淋巴细胞亚群和基因表达水平与心脏病类型、低钙血症和感染频率等临床表型无明显相关性。这些结果表明，在22q11.2缺失患者的T淋巴细胞减少症变得不那么严重，随着年龄的变化下的次要子集的组成。在有限的T细胞池中平衡的细胞因子谱可能代表胸腺缺陷综合征的T细胞稳态。
Chromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3(+), CD4(+), T cell receptor (TCR)alpha beta(+) or CD8 alpha alpha(+) cell counts were lower, and CD56(+) cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3(+) or CD4(+) cell counts was slower in patients than in controls. The proportion of CD8 alpha alpha(+) cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of V alpha 24(+) cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8 alpha alpha(+) cells was observed only in patients, and that with V alpha 24(+) cells was seen only in controls. No gene expression levels of interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome.