A dose-dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant.

A dose-dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant.
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DOI:
10.1084/jem.20052230
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发表时间:
2006-09-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Green JM
Green JM
中科院分区:
其他
文献类型:
--
作者:
Friend LD;Shah DD;Deppong C;Lin J;Bricker TL;Juehne TI;Rose CM;Green JM

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初始T细胞的活化需要通过抗原受体和CD 28整合信号。虽然人们对CD 28的重要性达成了一致,但对CD 28调节T细胞功能的机制仍存在争议。我们已经产生了一个基因靶向敲入小鼠表达突变的C-末端脯氨酸丰富的区域的胞质尾的CD 28。我们的分析最终表明,这个基序是必不可少的CD 28依赖性调节白细胞介素2的分泌和增殖。体内分析显示,在过敏性气道炎症模型中,该基序的突变解离了CD 28依赖性的细胞和体液应答调节。此外,我们发现了一个重要的基因剂量效应的突变表型,并提供了一个机制解释的矛盾数据的意义,这个基序在CD 28功能。
Activation of naive T cells requires the integration of signals through the antigen receptor and CD28. Although there is agreement on the importance of CD28, there remains controversy on the mechanism by which CD28 regulates T cell function. We have generated a gene-targeted knockin mouse expressing a mutation in the C-terminal proline-rich region of the cytoplasmic tail of CD28. Our analysis conclusively showed that this motif is essential for CD28-dependent regulation of interleukin 2 secretion and proliferation. In vivo analysis revealed that mutation of this motif-dissociated CD28-dependent regulation of cellular and humoral responses in an allergic airway inflammation model. Furthermore, we find an important gene dosage effect on the phenotype of the mutation and provide a mechanistic explanation for the conflicting data on the significance of this motif in CD28 function.
DOI: 10.1084/jem.190.3.375
发表时间: 1999-08-02
期刊: The Journal of experimental medicine
影响因子: --
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