A novel pathway of alloantigen presentation by dendritic cells
A novel pathway of alloantigen presentation by dendritic cells
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DOI：
10.4049/jimmunol.173.8.4828
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Lechler, RI
中科院分区：
文献类型：
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作者：
Herrera, OB;Golshayan, D;Lechler, RI
在移植的背景下，树突状细胞(DC)可以通过两种途径增敏同种异体反应性T细胞。直接途径是由供体DC呈递完整的供体MHC分子启动的。间接途径是受体树突状细胞将供体MHC加工成多肽的结果。这种简单的二分法表明，具有直接和间接同种异体特异性的T细胞不能相互交叉调节，因为涉及不同的APC。在这项研究中，我们描述了树突状细胞呈递MHC同种异体抗原的第三种半直接途径，挑战了这一结论。当小鼠DC与同种异体DC或内皮细胞共培养时，可以获得大量的I类和II类MHC：以依赖于温度和能量的方式。最重要的是，体内的获得性同种异体MHC在迁移到区域淋巴结后发生。通过抗体染色检测获得的MHC分子，并在体外诱导抗原特异性T细胞增殖。这些数据表明，由于获得供体MHC分子，受体DC可能将T细胞与直接和间接同种异体特异性联系在一起。
In the context of transplantation, dendritic cells (DCs) can sensitize alloreactive T cells via two pathways. The direct pathway is initiated by donor DCs presenting intact donor MHC molecules. The indirect pathway results from recipient DCs processing and presenting donor MHC as peptide. This simple dichotomy suggests that T cells with direct and indirect allospecificity cannot cross-regulate each other because distinct APCs are involved. In this study we describe a third, semidirect pathway of MHC alloantigen presentation by DCs that challenges this conclusion. Mouse DCs, when cocultured with allogeneic DCs or endothelial cells, acquired substantial levels of class I and class II MHC:peptide complexes in a temperature- and energy-dependent manner. Most importantly, DO acquired allogeneic MHC in vivo upon migration to regional lymph nodes. The acquired MHC molecules were detected by Ab staining and induced proliferation of Ag-specific T cells in vitro. These data suggest that recipient DCs, due to acquisition of donor MHC molecules, may link T cells with direct and indirect allospecificity.