Antigen-specific effector CD4 T lymphocytes school lamina propria dendritic cells to transfer innate tolerance.
Antigen-specific effector CD4 T lymphocytes school lamina propria dendritic cells to transfer innate tolerance.
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DOI：
10.4049/jimmunol.1203552
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
Zaghouani H
中科院分区：
文献类型：
--
作者：
Cascio JA;Haymaker CL;Divekar RD;Zaghouani S;Khairallah MT;Wan X;Rowland LM;Dhakal M;Chen W;Zaghouani H
树突状细胞（Dendritic cells，DC）在口服耐受中发挥重要作用，其产生抗炎细胞因子和诱导抑制性T调节细胞的能力与此相关。在此，我们证明了口服Ag后，固有层（LP）DCs参与特异性T细胞，并获得一种新的机制，通过这种机制，它们可以转移对不同T细胞特异性的耐受性。事实上，当携带髓鞘少突胶质细胞糖蛋白（MOG）35-55表位的Ig-MOG口服给药到T细胞充足或缺乏的小鼠中时，只有T细胞充足的宿主产生能够将耐受性转移到多种MHC II类限制性效应T细胞的CD 8 α+和CD 8 α− LP DC。令人惊讶的是，这些LP DC在与MOG特异性T细胞的初始相互作用期间上调程序性细胞死亡配体1（PD-L1），并利用这种抑制性分子来抑制T细胞的活化，而不管Ag特异性如何。此外，口服Ig-MOG能够克服用中枢神经系统（CNS）匀浆诱导的实验性过敏性脑脊髓炎（EAE），表明DC能够调节涉及不同T细胞特异性的疾病。这种以前未认识到的属性增强了DC对自身免疫的抵抗力。
Dendritic cells (DCs) have been shown to play a major role in oral tolerance and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive T regulatory cells. Herein, we demonstrate that upon oral administration of Ag, lamina propia (LP) DCs engage specific T cells and acquire a novel mechanism by which they transfer tolerance against diverse T cell specificities. Indeed, when Ig-MOG carrying the myelin oligodendrocyte glycoprotein (MOG)35–55 epitope was orally administered into either T cell sufficient or deficient mice, only the T cell sufficient hosts yielded CD8α+ and CD8α− LP DCs that were able to transfer tolerance to a variety of MHC class II-restricted effector T cells. Surprisingly, these LP DCs up-regulated programmed cell death ligand 1 (PD-L1) during the initial interaction with MOG-specific T cells and utilized this inhibitory molecule to suppress activation of T cells regardless of Ag specificity. Furthermore, oral Ig-MOG was able to overcome experimental allergic encephalomyelitis (EAE) induced with central nervous system (CNS) homogenate, indicating that the DCs are able to modulate disease involving diverse T cell specificities. This previously unrecognized attribute potentiates DCs against autoimmunity.
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DOI：
10.1084/jem.190.2.229
发表时间：
1999-07-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iwasaki A;Kelsall BL
通讯作者：
Kelsall BL
影响因子：
15.3
作者：
Legge, KL;Min, B;Zaghouani, H
通讯作者：
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影响因子：
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作者：
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通讯作者：
Jevnikar, AM
影响因子：
29.4
作者：
Lelouard, Hugues;Fallet, Mathieu;Gorvel, Jean-Pierre
通讯作者：
Gorvel, Jean-Pierre
影响因子：
--
作者：
Lefrancois, L;Lycke, N
通讯作者：
Lycke, N