Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein.
Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein.
复制标题
非造血细胞的交叉呈递和造血细胞的直接呈递诱导对髓磷脂碱性蛋白的中枢耐受。
DOI：
10.1073/pnas.0804970105
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发表时间：
2008
影响因子：
11.1
通讯作者：
Goverman,JoanM
中科院分区：
文献类型：
--
作者：
Perchellet,Antoine;Brabb,Thea;Goverman,JoanM
中枢耐受在消除外周抗原特异性自身反应性 T 细胞方面发挥着关键作用。在这里，我们表明，MHC I 类限制性 T 细胞对经典髓鞘碱性蛋白 (MBP)（髓鞘的一个组成部分）具有特异性，其中枢耐受性是由骨髓 (BM) 来源的细胞和非骨髓来源的细胞介导的。出乎意料的是，BM来源的细胞通过使用它们合成的经典MBP直接诱导耐受，而非BM来源的细胞通过交叉呈递从外源获得的经典MBP来介导耐受。因此，对组织特异性抗原的耐受可能涉及胸腺中的多种细胞类型和机制，这可能解释了当组织特异性抗原的表达仅在胸腺上皮细胞中受损时观察到的有限范围的自身免疫综合征。
Central tolerance plays a critical role in eliminating self-reactive T cells specific for peripheral antigens. Here we show that central tolerance of MHC class I-restricted T cells specific for classic myelin basic protein (MBP), a component of the myelin sheath, is mediated by both bone marrow (BM)-derived and nonBM-derived cells. Unexpectedly, BM-derived cells induce tolerance directly by using classic MBP that they synthesize, whereas nonBM-derived cells mediate tolerance by crosspresenting classic MBP acquired from an exogenous source. Thus, tolerance to tissue-specific antigens can involve multiple cell types and mechanisms in the thymus, which may account for the limited spectrum of autoimmune syndromes observed when expression of tissue-specific antigens is impaired only in thymic epithelial cells.