Cobbold Stephen P
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Expert Opin Ther Targets. 2002 Oct;6(5):583-99. doi: 10.1517/14728222.6.5.583.
It is now possible to induce donor-specific transplantation tolerance in adult rodents using a number of therapeutic strategies. These include the use of non-depleting monoclonal antibodies against T cell co-receptor and costimulation molecules, and immunisation with tolerogenic antigen-presenting cells. It is a common finding to all of these models of peripheral tolerance, as well as to various mouse models of autoimmune disease, that regulatory CD4(+) T cells are the principle mediators. There are currently no specific markers for regulatory T cells and their activity has been associated with different T cell subsets defined by the expression of activation markers, such as CD25 and cytotoxic T lymphocyte antigen-4 (CTLA-4), or anti-inflammatory cytokines, such as IL-10 and TGF-beta. Differential gene expression analyses have been used to identify potential new markers for regulatory T cells and to find novel targets for therapeutic manipulation of the immune system. The challenge now is to understand the biological principles that allow such immune reprogramming so that they can be safely applied to clinical situations.
现在，使用多种治疗策略在成年啮齿动物中诱导供体特异性移植耐受已成为可能。这些策略包括使用针对T细胞共受体和共刺激分子的非耗竭性单克隆抗体，以及用耐受性抗原呈递细胞进行免疫。在所有这些外周耐受模型以及各种自身免疫性疾病小鼠模型中，一个共同的发现是调节性CD4(+) T细胞是主要的介导者。目前尚无调节性T细胞的特异性标志物，其活性与由激活标志物（如CD25和细胞毒性T淋巴细胞抗原-4 (CTLA-4)）或抗炎细胞因子（如IL-10和TGF-β）表达所定义的不同T细胞亚群相关。差异基因表达分析已被用于识别调节性T细胞的潜在新标志物，并寻找免疫系统治疗性操纵的新靶点。现在面临的挑战是理解允许这种免疫重编程的生物学原理，以便能够安全地应用于临床情况。
