Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo.
Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo.
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DOI：
10.1084/jem.185.3.541
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发表时间：
1997-02-03
期刊：
影响因子：
--
通讯作者：
Karjalainen K
中科院分区：
文献类型：
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作者：
Brocker T;Riedinger M;Karjalainen K
淋巴样树突状细胞（DC）在免疫系统中发挥着重要作用。除了它们作为初级T细胞应答的有效诱导物的作用之外，DC似乎在胸腺细胞发育期间作为胸腺中的主要组织相容性复合物（MHC）II类+“交错细胞”发挥关键作用。胸腺DC与免疫耐受诱导有关，也有学者认为其与胸腺细胞的主要组织相容性复合物限制有关。我们大多数关于胸腺DC的知识都是使用高侵袭性和操作性的实验方案获得的，如胸腺再聚集培养、悬浮培养、胸腺移植和骨髓重建实验。这些研究中使用的DC必须经过广泛的分离程序或与重组生长因子一起培养。由于这些在体外操作后的DC的功能已被报道是不相同的DC在体内，我们打算建立一个系统，使我们能够调查DC功能，避免人为的干扰，由于处理。在这里，我们提出了一个转基因小鼠模型，在该模型中，我们靶向基因表达特异性DC。使用CD 11 c启动子，我们表达的MHC II类I-E分子特异性DC的所有组织，但不对其他类型的细胞。我们报道胸腺DC上的I-E表达足以阴性选择I-E反应性CD 4 + T细胞，并且在不完全的程度上选择CD 8 + T细胞。相反，如果只有DC表达I-E在II类缺陷的背景下，不能观察到CD 4 + T细胞的阳性选择。因此，DC可以在体内诱导阴性而非阳性选择事件。
It is well established that lymphoid dendritic cells (DC) play an important role in the immune system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ “interdigitating cells” in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those studies had to go through extensive isolation procedures or were cultured with recombinant growth factors. Since the functions of DC after these in vitro manipulations have been reported to be not identical to those of DC in vivo, we intended to establish a system that would allow us to investigate DC function avoiding artificial interferences due to handling. Here we present a transgenic mouse model in which we targeted gene expression specifically to DC. Using the CD11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, if only DC expressed I-E in a class II–deficient background, positive selection of CD4+ T cells could not be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.