T-cell tolerance: central and peripheral.

T-cell tolerance: central and peripheral.
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DOI:
10.1101/cshperspect.a006957
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发表时间:
2012-06-01
影响因子:
7.2
通讯作者:
Hogquist KA
Hogquist KA
中科院分区:
生物学1区
文献类型:
--
作者:
Xing Y;Hogquist KA

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未成熟胸腺细胞中 TCR 基因的体细胞重组导致一些细胞具有有用的 TCR 特异性,但也有许多细胞具有无用或潜在的自身反应特异性。因此,胸腺选择机制的作用是塑造 T 细胞库。具有对自肽-MHC复合物亲和力低的TCR的胸腺细胞被积极选择以进一步分化并在适应性免疫中发挥作用,而无用的胸腺细胞则因忽视而死亡。克隆缺失和克隆转移(Treg 分化)是胸腺中消除或控制自身反应性 T 细胞的主要过程。尽管这些过程被认为是有效的,但它们不足以在所有情况下发挥作用。因此,存在外周耐受过程,其中自身反应性T细胞变得功能性无反应(无反应性)或在遇到胸腺外的自身抗原后被删除。中枢和外周 T 细胞耐受机制研究的最新进展正在促进治疗自身免疫性疾病和癌症以及改善移植结果的治疗策略的发展。
Somatic recombination of TCR genes in immature thymocytes results in some cells with useful TCR specificities, but also many with useless or potentially self-reactive specificities. Thus thymic selection mechanisms operate to shaper the T cell repertoire. Thymocytes that have a TCR with low affinity for self-peptide-MHC complexes are positively selected to further differentiate and function in adaptive immunity, whereas useless ones die by neglect. Clonal deletion and clonal diversion (Treg differentiation) are the major processes in the thymus that eliminate or control self-reactive T cells. Although these processes are thought to be efficient they are insufficient to in all circumstances. Thus, peripheral tolerance processes exists, wherein self-reactive T cells become functional unresponsive (anergy) or are deleted after encountering self-antigens outside of the thymus. Recent advances in mechanistic studies of central and peripheral T cell tolerance are promoting the development of therapeutic strategies to treat autoimmune disease and cancer and improve transplantation outcome.
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