Progression of armed CTL from draining lymph node to spleen shortly after localized infection with herpes simplex virus 1
Progression of armed CTL from draining lymph node to spleen shortly after localized infection with herpes simplex virus 1
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DOI：
10.4049/jimmunol.168.2.834
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发表时间：
2002-01-15
影响因子：
4.4
通讯作者：
Brooks, AG
中科院分区：
文献类型：
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作者：
Coles, RM;Mueller, SN;Brooks, AG
我们使用三种协调的体内T细胞追踪方法检测了单纯疱疹病毒1型(HSV-1)局部足垫感染后立即产生CTL免疫的情况。含有HSV-1糖蛋白B免疫优势肽的四聚体MHC-I类抗原显示，感染后第5天引流淋巴结内的抗原特异性T细胞比例达到高峰，2天后脾内的抗原特异性T细胞比例达到高峰。四聚体阳性细胞优先表达活化标记CD25，但不表达脾，提示特异性T细胞最初在淋巴结内被激活。体内细胞毒性试验表明，在感染后第2天，引流的淋巴结内就出现了抗原特异性效应细胞，在脾中检测到之前又延迟了2天。CFSE标记的gB转基因T细胞的过继转移与引流淋巴结中效应CTL的早期武装一致，表明它们在感染后第2天已经经历了一到四轮的细胞分裂。相反，在第4天，脾中首次检测到数量可观的增殖T细胞，当时它们已经经历了广泛的细胞分裂。这些数据表明，在HSV-1局部感染后不久，HSV-1特异性T细胞迅速激活并武装在引流淋巴结内。随后，它们扩散到其他间隔，如脾，在那里它们以不依赖于银的方式进一步增殖。
We have examined the generation of CTL immunity immediately after localized footpad infection with herpes simplex virus 1 (HSV-1) using three coordinated in vivo T cell tracking methodologies. Tetrameric MHC class I containing the immunodominant peptide from HSV-1 glycoprotein B (gB) showed that after infection the proportion of Ag-specific T cells peaked at day 5 within draining popliteal lymph nodes and 2 days later in the spleen. Preferential expression of the activation marker CD25 by tetramer-positive cells in draining popliteal nodes but not spleen suggested that gB-specific T cells were initially activated within the lymph node. In vivo cytotoxicity assays showed that Ag-specific effector cells were present within the draining lymph nodes as early as day 2 after infection, with a further 2-day lag before detection in the spleen. Consistent with the very early arming of effector CTL in the draining lymph node, adoptive transfer of CFSE-labeled gB-specific transgenic T cells showed that they had undergone one to four rounds of cell division by day 2 after infection. In contrast, proliferating T cells were first detected in appreciable numbers in the spleen on day 4, at which time they had undergone extensive cell division. These data demonstrate that HSV-1-specific T cells are rapidly activated and armed within draining lymph nodes shortly after localized HSV-1 infection. This is followed by their dissemination to other compartments such as the spleen, where they further proliferate in an Ag-independent fashion.