Jooss K, Gjata B, Danos O, von Boehmer H, Sarukhan A
Genethon III, 91002 Evry, France.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8738-43. doi: 10.1073/pnas.151088898. Epub 2001 Jul 3.
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.
有人提出，无反应性T细胞可能并非仅仅是惰性细胞，而是可能发挥积极作用，例如通过调节免疫反应。我们之前曾报道过，通过持续抗原刺激在体内产生的产生白细胞介素-10的“无反应性”CD4(+)T细胞的存在。利用一种基因转移系统，在该系统中，此类T细胞识别的抗原由两种不同的DNA病毒载体在骨骼肌中表达，我们发现这些细胞不仅对其同源抗原保持耐受，而且还能抑制幼稚T细胞针对免疫原性腺病毒蛋白的免疫反应。此外，它们能完全抑制因免疫反应而发生的组织破坏。这里介绍的系统具有独特性，因为T细胞已在体内失能，其抗原特异性和功能状态是已知的，并且抗原表达的量、形式和时间可以被操控。因此，这个模型将使我们能够仔细剖析这些无反应性T细胞调节幼稚T细胞启动和/或效应功能的机制。
