Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia
Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia
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DOI：
10.1093/intimm/12.4.449
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Autran, B
中科院分区：
文献类型：
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作者：
Hubert, P;Bergeron, F;Autran, B
特发性CD 4（+）淋巴细胞减少症（ICL）定义为在没有任何已知免疫缺陷原因的情况下CD 4（+）T细胞的稳定损失。这种综合征的病因至今尚未确定。它影响成年患者，其中一些人表现出类似于HIV感染者的机会性感染。细胞免疫缺陷可能是由于CD 3-TCR途径的生化故障的假设，在这里进行了研究，在一个病人的过程中发现的隐球菌脑膜炎的严重选择性CD 4（+）淋巴细胞减少症与CD 8（+）T细胞计数增加。仅在CD 4（+）亚群中观察到对CD 3-TCR刺激的T细胞增殖减少40%。CD 3诱导的蛋白酪氨酸磷酸化在CD 4（+）和CD 8（+）亚群中是保守的，T细胞蛋白酪氨酸激酶p56（Lck）、p59（Fyn）ZAP-70水平是正常的。然而，我们发现与健康对照供体相比，患者T细胞中的p56（Lck）激酶活性降低了50%，p59（Fyn）活性似乎没有改变，然而，我们没有发现p56（Lck）的任何遗传异常。因此，这些结果表明，一个未知的蛋白质调节p56（Lck）活性的缺陷发生在这个病人的T细胞。总之，这些发现揭示了ICL中p56（Lck）的改变，并证实了这种激酶在维持外周CD 4（+）T细胞亚群中的关键作用。
Idiopathic CD4(+) lymphocytopenia (ICL) is defined by a stable loss of CD4(+) T cells in the absence of any known cause of immune deficiency. This syndrome is still of undetermined origin. It affects adult patients, some of them displaying opportunistic infections similar to HIV-infected subjects. The hypothesis that the cellular immune defect may be due to biochemical failures of the CD3-TCR pathway is investigated here in a patient associating a severe selective CD4(+) lymphocytopenia with an increased CD8(+) T cell count discovered in the course of a cryptococcal meningitidis. A 40% reduction of T cell proliferation to CD3-TCR stimulation is observed only in the CD4(+) subpopulation. The early CD3-induced protein tyrosine phosphorylations are conserved in both CD4(+) and CD8(+) subsets, and the levels of the T cell protein tyrosine kinases p56(Lck), p59(Fyn) ZAP-70 are normal. However, we find a 50% reduction of p56(Lck) kinase activity in the patient's T cells compared to a healthy control donor, p59(Fyn) activity does not appear to be altered, Nevertheless, we do not find any genetic abnormality of p56(Lck). These results thus suggest that a defect of an unknown protein regulating p56(Lck) activity takes place in this patient's T cells. Taken together, these findings reveal p56(Lck) alteration in ICL and confirm the critical role of this kinase in the maintenance of the peripheral CD4(+) T cell subpopulation.