Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be rescued for full effector function
Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be rescued for full effector function
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DOI：
10.4049/jimmunol.175.2.855
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Melief, CJM
中科院分区：
文献类型：
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作者：
Dumortier, H;van Mierlo, GJD;Melief, CJM
未成熟的树突状细胞（DC）与其成熟的对应物相反，不能动员CD 8（+）CTL应答，相反，已报道诱导CTL耐受。我们通过将腺病毒肽负载的DC（D1细胞系）输注到接受了腺病毒特异性幼稚TCR转基因CD 8（+）T细胞的小鼠体内，直接研究了未成熟DC与成熟DC对CTL应答的影响。而静脉注射成熟的DC引发了剧烈的CTL扩增，未成熟的DC引起的增殖很少，只涉及少数的TCR转基因CTL。即使后者CTL开发的效应功能，包括细胞溶解活性和促炎细胞因子分泌，这些细胞显着不同的成熟DC引发的CTL，因为它们没有表现出下调的CD 62 L和CCR 7，受体参与T细胞在淋巴器官中的陷阱。有趣的是，过继转移的CTL效应细胞后收获的启动成熟或不成熟的DC到幼稚受体小鼠，然后暴露于腺病毒，产生定量和定性难以区分的CTL记忆反应。因此，未成熟DC在体内引发初始CD 8（+）T细胞，虽然不能诱导全面的全身性CTL应答，但导致中枢记忆样T细胞的形成，其能够在次级抗原刺激时扩增并产生IFN-γ。
Immature dendritic cells (DC), in contrast to their mature counterparts, are incapable of mobilizing a CD8(+) CTL response, and, instead, have been reported to induce CTL tolerance. We directly addressed the impact of immature vs mature DC on CTL responses by infusing adenovirus peptide-loaded DC (of the D1 cell line) into mice that had received adenovirus-specific naive TCR-transgenic CD8(+) T cells. Whereas i.v. injection of mature DC triggered vigorous CTL expansion, immature DC elicited little proliferation involving only a minority of the TCR-transgenic CTL. Even though the latter CTL developed effector functions, including cytolytic activity and proinflammatory cytokine secretion, these cells differed significantly from CTL primed by mature DC in that they did not exhibit down-regulation of CD62L and CCR7, receptors involved in trapping of T cells in the lymphoid organs. Interestingly, adoptive transfer of CTL effector cells harvested after priming by either mature or immature DC into naive recipient mice, followed by exposure to adenovirus, yielded quantitatively and qualitatively indistinguishable CTL memory responses. Therefore, in vivo priming of naive CD8(+) T cells by immature DC, although failing to induce a full-blown, systemic CTL response, resulted in the formation of central memory-like T cells that were able to expand and produce IFN-gamma upon secondary antigenic stimulation.