T cell tolerance in transplantation: possibilities for therapeutic intervention.
T cell tolerance in transplantation: possibilities for therapeutic intervention.
复制标题
DOI：
10.1517/14728222.6.5.583
复制
发表时间：
2002-10-01
影响因子：
5.8
通讯作者：
Cobbold, Stephen P
中科院分区：
文献类型：
--
作者：
Cobbold, Stephen P
现在有可能通过一些治疗策略在成年啮齿动物中诱导供者特异性移植耐受。这些措施包括使用针对T细胞共受体和共刺激分子的非耗竭单抗，以及用产生耐受性的抗原提呈细胞进行免疫。对于所有这些外周耐受模型以及各种自身免疫性疾病的小鼠模型来说，一个共同的发现是，调节性CD4(+)T细胞是主要的媒介。目前还没有调节性T细胞的特异性标志物，它们的活性与不同的T细胞亚群有关，活化标志物如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和转化生长因子-β。差异基因表达分析已被用于识别潜在的调节性T细胞的新标记，并为免疫系统的治疗操作寻找新的靶点。现在的挑战是理解允许这种免疫重新编程的生物学原理，以便它们能够安全地应用于临床情况。
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.