Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.
Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.
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DOI：
10.1038/ni.3327
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发表时间：
2016-02
影响因子：
30.5
通讯作者：
Jenkins MK
中科院分区：
文献类型：
--
作者：
Malhotra D;Linehan JL;Dileepan T;Lee YJ;Purtha WE;Lu JV;Nelson RW;Fife BT;Orr HT;Anderson MS;Hogquist KA;Jenkins MK
对小鼠单克隆CD4+ T细胞库的研究已经揭示了几种自身耐受机制，然而，在正常库中起作用的机制尚不清楚。在此，研究了对在不同器官中表达的绿色荧光蛋白特异性的多克隆CD4+ T细胞，从而确定特定表达模式对相同表位特异性T细胞的影响。胸腺抗原呈递细胞均匀呈递的肽被克隆删除所耐受，而胸腺排除的肽被忽略。胸腺表达有限的肽诱导部分克隆缺失和受损的效应，但增强调节性T细胞的潜力。这些机制也对内源性表达的自身抗原特异性的T细胞群体具有活性。因此，根据自身肽表达模式，多克隆CD4+ T细胞的免疫耐受性通过不同的机制维持。
Studies of mouse monoclonal CD4+ T cell repertoires have revealed several mechanisms of self-tolerance, however, which mechanisms operate in normal repertoires is unclear. Here, polyclonal CD4+ T cells specific for green fluorescent protein expressed in different organs were studied, allowing determination of the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas thymus-excluded peptides were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self-antigens. Thus, immune tolerance of polyclonal CD4+ T cells is maintained by distinct mechanisms, according to self-peptide expression patterns.