Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model
Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model
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DOI：
10.4049/jimmunol.164.6.2937
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发表时间：
2000-03-15
影响因子：
4.4
通讯作者：
Fazekas de St Groth, B
中科院分区：
文献类型：
--
作者：
Lambrecht, BN;Pauwels, RA;Fazekas de St Groth, B
树突状细胞（DC）被认为是负责致敏吸入Ag和诱导肺中的适应性免疫。将银脉冲的骨髓来源的DC转移到幼稚小鼠的气道中后，研究肺中T细胞活化的特征。体内Ag特异性T细胞的细胞分裂在羧基荧光素二乙酸琥珀酰亚胺酯标记的幼稚蛾细胞色素c反应性TOR转基因T细胞的队列中进行。我们的过继转移系统是这样的，即转移的DC是表达将细胞色素c呈递给转基因T细胞所需的MHC分子的唯一细胞。Ag特异性T细胞活化和增殖在肺引流淋巴结中迅速发生，而在非引流淋巴结或脾中不发生。未诱导非Ag特异性T细胞的旁观者活化。Ag特异性T细胞的分裂伴随着CD69的瞬时表达，而CD44的上调随着每次细胞分裂而增加。在反应的第4天，分裂的细胞已再循环至非引流淋巴结和脾脏。在体外再刺激与特定的Ag显示，T细胞被引发增殖更强烈，并产生更高的细胞因子每细胞的量。这些数据与肺中的DC在从不同的库中选择Ag反应性T细胞方面极其有效的概念一致。这种反应最初局限于纵隔淋巴结，但随后扩散到全身，该系统应允许我们研究导致吸入Ag致敏的早期事件。
Dendritic cells (DCs) are thought to be responsible for sensitization to inhaled Ag and induction of adaptive immunity in the lung. The characteristics of T cell activation in the lung were studied after transfer of Ag-pulsed bone marrow-derived DCs into the airways of naive mice. Cell division of Ag-specific T cells in vivo was followed in a carboxyfluorescein diacetate succinimidyl ester-labeled cohort of naive moth cytochrome c-reactive TOR transgenic T cells, Our adoptive transfer system was such that transferred DCs were the only cells expressing the MHC molecule required for presentation of cytochrome c to transgenic T cells. Ag-specific T cell activation and proliferation occurred rapidly ire the draining lymph nodes of the lung, but not in nondraining lymph nodes or spleen. No bystander activation of non-Ag-specific T cells was induced. Division of Ag-specific T cells was accompanied by transient expression of CD69, while up-regulation of CD44 increased with each cell division. Divided cells had recirculated to nondraining lymph nodes and spleen by day 4 of the response. In vitro restimulation with specific Ag revealed that T cells were primed to proliferate more strongly and to produce higher amounts of cytokines per cell. These data are consistent with the notion that DCs in the lung are extremely efficient in selecting Ag-reactive T cells from a diverse repertoire. The response is initially localized in the mediastinal lymph nodes, but subsequently spreads systemically, This system should allow us to study the early events leading to sensitization to inhaled Ag.