Severe combined immunodeficiency caused by deficiency in either the δ or the ε subunit of CD3
Severe combined immunodeficiency caused by deficiency in either the δ or the ε subunit of CD3
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DOI：
10.1172/jci200422588
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发表时间：
2004-11-01
影响因子：
15.9
通讯作者：
Le Deist, F
中科院分区：
文献类型：
--
作者：
de Saint Basile, G;Geissmann, F;Le Deist, F
我们研究了严重联合免疫缺陷的分子机制，其特征是选择性和完全缺乏T细胞。3个家系中的3例患者和2例胎儿均出现了这种情况。对3个家族进行的连锁分析显示，患者在11 q23区域内携带纯合单倍型，其中编码CD 3D的γ、δ和γ亚基的基因位于该区域。来自2个家族的患者和受累胎儿为CD 3D基因突变纯合子，来自第3个家族的患者为CD 3D基因突变纯合子。对来自CD 3 δ缺陷胎儿的胸腺进行了分析，发现T细胞分化在进入双阳性（CD 4（+）CD 8（+））阶段时被阻断，中间CD 4-单阳性细胞积累。这表明CD 3 δ在促进早期胸腺细胞向双阳性阶段发展中起重要作用。总而言之，这些发现将严重联合免疫缺陷的已知分子机制扩展到一种新的缺陷，即，CD 3 δ亚基在人胸腺细胞发育中起重要作用，因为这些亚基与前TCR和TCR相关。
We investigated the molecular mechanism underlying a severe combined immunodeficiency characterized by the selective and complete absence of T cells. The condition was found in S patients and 2 fetuses from 3 consanguineous families. Linkage analysis performed on the 3 families revealed that the patients were carrying homozygous haplotypes within the 11q23 region, in which the genes encoding the gamma, delta, and epsilon subunits of CD3D are located. Patients and affected fetuses from 2 families were homozygous for a mutation in the CD3D gene, and patients from the third family were homozygous for a mutation in the CD3epsilon gene. The thymus from a CD3delta-deficient fetus was analyzed and revealed that T cell differentiation was blocked at entry into the double positive (CD4(+)CD8(+)) stage with the accumulation of intermediate CD4-single positive cells. This indicates that CD3delta plays an essential role in promoting progression of early thymocytes toward double-positive stage. Altogether, these findings extend the known molecular mechanisms underlying severe combined immunodeficiency to a new deficiency, i.e., CD3epsilon deficiency, and emphasize the essential roles played by the CD3epsilon and CD3delta subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR.