In vivo detection of dendritic cell antigen presentation to CD4(+) T cells.
In vivo detection of dendritic cell antigen presentation to CD4(+) T cells.
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DOI：
10.1084/jem.185.12.2133
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发表时间：
1997-06-16
期刊：
影响因子：
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通讯作者：
Jenkins MK
中科院分区：
文献类型：
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作者：
Ingulli E;Mondino A;Khoruts A;Jenkins MK
虽然淋巴树突状细胞（DC）被认为在T细胞活化中发挥重要作用，但在体内从未直接观察到抗原携带DC和抗原特异性T细胞之间的初始物理相互作用，在这种情况下，可以明确评估应答T细胞对相关抗原的特异性。我们使用共聚焦显微镜跟踪荧光染料标记的DC和幼稚TCR转基因CD 4 + T细胞的体内位置特异性的OVA肽-I-Ad复合物过继转移到同基因受体。未暴露于OVA肽的DC归巢于淋巴结的副皮质区，但不与OVA肽特异性T细胞相互作用。相比之下，OVA肽特异性T细胞在注射前用OVA肽体外脉冲的旁皮质DC周围形成大簇。在给予完整的OVA后，还观察到受体的副皮质DC与OVA肽特异性T细胞之间的相互作用。注射OVA肽脉冲的DC导致特异性T细胞在体内产生IL-2，增殖并分化为能够引起迟发型超敏反应的效应细胞。令人惊讶的是，注射后48小时，经OVA肽脉冲的DC（而不是未经脉冲的DC）从含有转移的TCR转基因群体的小鼠的淋巴结中消失。这些结果表明，携带抗原的DC直接与淋巴结富含T细胞区域内的幼稚抗原特异性T细胞相互作用。这种相互作用导致T细胞活化和DC消失。
Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.