Peripheral priming of alloreactive T cells by the direct pathway of allorecognition
Peripheral priming of alloreactive T cells by the direct pathway of allorecognition
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DOI：
10.1002/eji.200425309
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Daniel, C
中科院分区：
文献类型：
--
作者：
Baratin, M;Bonin, K;Daniel, C
最近的研究，虽然有争议，已经表明，次级淋巴器官可能不构成一个重要的网站为移植抗原的免疫反应的启动。然而，这个问题从来没有在直接和间接的同种异体识别的背景下进行过研究。在这里，我们的特点是在引流淋巴结和皮肤移植物中产生的免疫反应，在一个小鼠模型的基础上，一个单一的T细胞克隆型，这两个途径可以独立研究。在该模型中，直接或间接途径的移植物排斥反应发生类似的动力学，虽然同种异体反应的启动是明显不同的。在间接反应期间，在移植后第7天，在引流淋巴结中首次观察到同种异体反应性T细胞的扩增和活化，随后在第11天观察到移植物浸润性T细胞。与此形成鲜明对比的是，直接激活的同种异体反应性T细胞在移植物内的早期阶段被检测到，并且仅在皮肤移植物排斥反应几乎完成后的引流淋巴结中被检测到。这些结果表明，通过直接途径的幼稚T细胞的敏化可以发生在次级淋巴器官外。
Recent studies, though controversial, have suggested that secondary lymphoid organs may not constitute an essential site for the initiation of immune responses to transplant antigens. However, this issue has never been examined in the context of direct and indirect allorecognition. Here, we characterized immune responses arising in draining lymph nodes and skin allografts, in a murine model based on a single T cell clonotype where these two pathways can be independently studied. In this model, graft rejection by the direct or the indirect pathway occurred with similar kinetics, although initiation of the alloreactive responses was clearly different. During indirect responses, expansion and activation of alloreactive T cells were first observed in draining lymph nodes, at day 7 post-transplant, and graft-infiltrating T cells were observed later, at day 11. In striking contrast, directly activated alloreactive T cells were detected at an early stage inside the graft, and only later in the draining lymph nodes, after skin allograft rejection was almost completed. These results suggest that sensitization of naive T cells through the direct pathway could take place outside secondary lymphoid organs.