Recall and propagation of allospecific memory T cells independent of secondary lymphoid organs
Recall and propagation of allospecific memory T cells independent of secondary lymphoid organs
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DOI：
10.1073/pnas.092596999
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发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Lakkis, FG
中科院分区：
文献类型：
--
作者：
Chalasani, G;Dai, ZH;Lakkis, FG
对移植器官有反应的同种异体T细胞群包括幼稚淋巴细胞和记忆淋巴细胞。虽然已经确定幼稚T细胞可被次级淋巴器官（脾、淋巴结和粘膜淋巴组织）有组织结构内的抗原激活，但记忆T细胞的激活和繁殖是否依赖于这些器官的归巢尚不清楚。为了回答这个问题，我们研究了同种异体幼稚T细胞或记忆T细胞是否可以介导缺乏所有次要淋巴组织的突变小鼠的急性同种异体心脏移植排斥反应。我们的实验结果表明，抗原经历记忆T细胞比幼稚T细胞有两个优势：(i)记忆T细胞产生强烈的免疫反应，导致不依赖于次级淋巴器官的同种异体移植排斥；记忆T细胞产生更多的记忆T细胞而不归巢到次级淋巴器官。记忆T细胞的这些独特特性被进一步证实，表明在没有抗原刺激的情况下由初始T细胞的稳态增殖产生的记忆样T细胞在排斥同种异体移植物时不理想，并且在缺乏次级淋巴组织的小鼠中不产生记忆T细胞。
The allospecifc T cell population responding to a transplanted organ consists of both naive and memory lymphocytes. Although it is established that naive T cells are activated by antigen within the organized structures of secondary lymphoid organs (the spleen, lymph nodes, and mucosal lympoid tissues), it is not clear whether memory T cell activation and propagation depend on homing to these organs. To answer this question, we investigated whether allospecific naive or memory T cells can mediate acute cardiac allograft rejection in mutant mice that lack all of their secondary lymphoid tissues. The results of our experiments demonstrated that antigen-experienced memory T cells have two advantages over naive T cells: (i) memory T cells mount a vigorous immune response that leads to allograft rejection independent of secondary lymphoid organs; and (it) memory T cells generate more memory T cells without homing to secondary lymphoid organs. These unique properties of memory T cells were further confirmed by showing that memory-like T cells that arise from the homeostatic proliferation of naive T cells in the absence of antigenic stimulation are suboptimal at rejecting allografts and do not generate memory T cells in mice devoid of secondary lymphoid tissues.