Defective expression of p56lck in an infant with severe combined immunodeficiency
Defective expression of p56lck in an infant with severe combined immunodeficiency
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DOI：
10.1172/jci3205
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发表时间：
1998-07-15
影响因子：
15.9
通讯作者：
Taylor, N
中科院分区：
文献类型：
--
作者：
Goldman, FD;Ballas, ZK;Taylor, N
严重联合免疫缺陷（SCID）是一种异质性疾病，其特征是细胞和体液免疫的严重缺陷。我们在此报告一个婴儿的临床和实验室特征的SCID和选择性CD4淋巴细胞减少和缺乏CD28表达的CD8(+) T细胞。该患者的T细胞对各种有丝分裂原和IL-2表现出较差的成母反应。其他T细胞抗原受体诱导的反应，包括CD69的上调，也同样受到抑制。然而，更多的近端T细胞抗原受体信号事件，如抗cd3诱导的蛋白酪氨酸磷酸化、丝裂原相关蛋白激酶磷酸化和钙动员是完整的。虽然p59fyn和ZAP-70蛋白酪氨酸激酶在正常水平表达，但p56lck水平明显下降。此外，这种减少与缺乏外显子7激酶编码域的选择性剪接的lck转录物的存在有关。这些数据表明p56lck表达不足可以在人类中产生SCID表型。
Severe combined immune deficiency (SCID) is a heterogeneous disorder characterized by profound defects in cellular and humoral immunity. We report here an infant with clinical and laboratory features of SCID and selective CD4 lymphopenia and lack of CD28 expression on CD8(+) T cells. T cells from this patient showed poor blastogenic responses to various mitogens and IL-2. Other T cell antigen receptor-induced responses, including upregulation of CD69, were similarly inhibited. However, more proximal T cell antigen receptor signaling events, such as anti-CD3 induced protein tyrosine phosphorylation, phosphorylation of mitogen-associated protein kinase, and calcium mobilization were intact. Although p59fyn and ZAP-70 protein tyrosine kinases were expressed at normal levels, a marked decrease in the level of p56lck was noted. Furthermore, this decrease was associated with the presence of an alternatively spliced lck transcript lacking the exon 7 kinase encoding domain. These data suggest that a deficiency in p56lck expression can produce a SCID phenotype in humans.