Functional redundancy between thymic CD8α+ and Sirpα+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins.

Functional redundancy between thymic CD8α+ and Sirpα+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins.
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DOI:
10.4049/jimmunol.1002587
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发表时间:
2011-02-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Unanue ER
Unanue ER
中科院分区:
其他
文献类型:
--
作者:
Atibalentja DF;Murphy KM;Unanue ER

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我们评估了胸腺中的抗原提呈细胞(APC)对血源性蛋白抗原的提呈。两种常见的树突状细胞,CD8α+Sirpα−CD11chi(CD8α+CDC)和CD8α−Sirpα+CD11chi细胞(Sirpα+CDC)是从静脉注射的蛋清溶菌酶中产生II类MHC结合肽的细胞。所有胸腺APC都获得了注射的HEL,其中以浆细胞样树突状细胞(PDC)最好,其次是Sirpα+CDC和CD8α+CDC。CDC在HEL T细胞受体(TCR)转基因小鼠中诱导了相似程度的阴性选择和Tregs,表明这两个CDC亚群在血源性HEL中发挥了多余的作用。不成熟的DC或PDC的效率要低得多。BATF3型−/−小鼠CD8CD8CD8+CDC数显著减少,胸腺APC的I-AK分子对α提呈功能无明显影响。最后,氯膦酸盐脂质体(COLD-LIP)处理TCR转基因小鼠可耗尽包括Sirpα+CDC在内的全血APC,但不影响胸腺APC的数量。在这种处理的小鼠中,当给予HEL时,对小鼠的阴性选择或Tregs没有影响,表明T细胞反应主要由定位于胸腺的CDC介导。
We evaluated the presentation of blood-derived protein antigens by antigen presenting cells (APC) in the thymus. Two conventional dendritic cells (cDC), the CD8α+Sirpα−CD11chi (CD8α+cDC) and the CD8α−Sirpα+ CD11chi cells (Sirpα+cDC), were previously identified as presenting class II-MHC bound peptides from hen egg-white lysozyme (HEL) injected intravenously. All thymic APC acquired the injected HEL, with the plasmacytoid DC (pDC) being the best, followed by the Sirpα+ cDC and the CD8α+cDC. Both cDC induced to similar extent negative selection and Tregs in HEL T cell receptor (TCR) transgenic mice, indicating a redundant role of the two cDC subsets in the presentation of blood-borne HEL. Immature DC or pDC were considerably less efficient. Batf3−/− mice, with significantly reduced numbers of CD8α+cDC, were not impaired in HEL presentation by I-Ak molecules of thymic APC. Lastly, clodronate-liposome (CLOD-LIP) treatment of TCR transgenic mice depleted blood APC including Sirpα+ cDC, without affecting the number of thymic APC. In such treated mice there was no effect on negative selection or Tregs in mice when administering HEL, indicating that the T cell responses were mediated primarily by the cDC localized in the thymus.
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