Developmental changes of FOXP3-expressing CD4+CD25+ regulatory T cells and their impairment in patients with FOXP3 gene mutations
Developmental changes of FOXP3-expressing CD4+CD25+ regulatory T cells and their impairment in patients with FOXP3 gene mutations
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DOI：
10.1016/j.clim.2007.08.004
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发表时间：
2007-12-01
影响因子：
8.6
通讯作者：
Miyawaki, Toshio
中科院分区：
文献类型：
--
作者：
Fuchizawa, Tatsuya;Adachi, Yuichi;Miyawaki, Toshio
FOXP 3是CD 4（+）CD 25（+）调节性T（Treg）细胞产生和功能所必需的。为了阐明Treg细胞的生物学作用，我们使用单克隆抗FOXP 3抗体来检查儿童发育期间Treg细胞的频率。CD 4（+）CD 25（+）FOXP 3（+）T细胞的百分比从出生后不久到成年期是恒定的。脐血中CD 4（+）CD 25（+）FOXP 3（+）T细胞表现为幼稚型CD 45 RA（+）CD 45 RO（-）表型，而成人CD 4（+）CD 25（+）FOXP 3（+）T细胞主要表现为记忆型CD 45 RA（-）CD 45 RO（+）表型。记忆性CD 4（+）CD 25（+）FOXP 3 T细胞的年龄依赖性优势意味着初始和记忆性Treg细胞之间的功能差异。值得注意的是，4例FOXP 3基因突变患者显示缺乏CD 4（+）CD 25（+）FOXP 3（+）T细胞。重要的是，一名具有移码突变的患者表现出IPEX的典型症状（免疫失调，多内分泌病，肠病，X连锁），表现出明显的T细胞活化，而其他具有错义突变的患者，临床上更温和，没有。这一观察结果表明IPEX中可能存在基因型-表型相关性。(c)2007年爱思唯尔公司All rights reserved.
FOXP3 is required for the generation and function of CD4(+)CD25(+) regulatory T (Treg) cells. To elucidate the biological role of Treg cells, we used a monoclonal anti-FOXP3 antibody to examine the frequencies of Treg cells, during child development. The percentages of CD4(+)CD25(+)FOXP3(+) T cells were constant shortly from after birth through adulthood. CD4(+)CD25(+)FOXP3(+) T cells in cord blood showed the naive CD45RA(+)CD45RO(-) phenotype, whereas adult CD4(+)CD25(+)FOXP3(+) T cells expressed mostly the memory CD45RA(-)CD45RO(+) phenotype. The age-dependent dominance of memory CD4(+)CD25(+)FOXP3 T cells implies functional differences between naive and memory Treg cells. Notably, four patients with FOXP3 gene mutations revealed a paucity of CD4(+)CD25(+)FOXP3(+) T cells. Importantly, one patient with a frame shift mutation, who showed typical symptoms of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), exhibited marked T cell activation, whereas others with missense mutations, who were clinically milder, did not. This observation suggests a possible genotype-phenotype correlation in IPEX. (c) 2007 Elsevier Inc. All rights reserved.