Regulatory function of in vivo anergized CD4+ T cells

Regulatory function of in vivo anergized CD4+ T cells
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DOI:
10.1073/pnas.151088898
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发表时间:
2001-07-17
影响因子:
11.1
通讯作者:
Sarukhan, A
Sarukhan, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Jooss, K;Gjata, B;Sarukhan, A

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已经表明,无反应性T细胞可能不仅是惰性细胞,而且可能发挥积极作用,例如通过调节免疫应答。我们以前曾报道过在体内通过连续抗原刺激产生的“无反应性”IL-10产生的CD 4(+)T细胞的存在。使用基因转移系统,其中由这样的T细胞识别的抗原通过两种不同的DNA病毒载体在骨骼肌中表达,我们表明,这些细胞不仅保持对它们的同源抗原的耐受性,而且可以抑制幼稚T细胞对免疫原性腺病毒蛋白的免疫应答。此外,它们可以完全抑制由于免疫应答而发生的组织破坏。这里提出的系统是独特的,因为T细胞已经在体内无能量化,它们的抗原特异性和功能状态是已知的,并且可以操纵抗原表达的量、形式和时间。因此,该模型将允许我们仔细剖析这些无反应性T细胞调节初始T细胞的引发和/或效应子功能的机制。
It has been suggested that anergic T cells may not be only inert cells but may rather play an active role, for example by regulating immune responses. We have previously reported the existence of "anergic" IL-10-producing CD4(+) T cells generated in vivo by continuous antigenic stimulation. Using a gene transfer system where the antigen recognized by such T cells is expressed in skeletal muscle by two different DNA viral vectors, we show that these cells not only remain tolerant toward their cognate antigen but also can suppress the immune response of naive T cells against the immunogenic adenoviral proteins. Furthermore, they can completely inhibit tissue destruction that takes place as a result of an immune response. The system presented here is unique in that the T cells have been anergized in vivo, their antigen specificity and functional status are known, and the amount, form, and timing of antigen expression can be manipulated. This model will therefore permit us to carefully dissect the mechanisms by which these anergic T cells regulate the priming and/or effector function of naive T cells.