Jiang Janina Q, He Xiao-Song, Feng Ningguo, Greenberg Harry B
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
J Virol. 2008 Jul;82(14):6812-9. doi: 10.1128/JVI.00450-08. Epub 2008 May 14.
CD8 T-cell response provides an important defense against rotavirus, which infects a variety of systemic locations in addition to the gut. Here we investigated the distribution, phenotype, and function of rotavirus-specific CD8 T cells in multiple organs after rotavirus infection initiated via the intranasal, oral, or intramuscular route. The highest level of virus-specific CD8 T cells was observed in the Peyer's patches of orally infected mice and in the lungs of intranasally infected animals. Very low levels of virus-specific CD8 T cells were detected in peripheral blood or spleen irrespective of the route of infection. Rotavirus-specific CD8 T cells from Peyer's patches of orally infected mice expressed high levels of CCR9, while CXCR6 and LFA-1 expression was associated with virus-specific CD8 T cells in lungs of intranasally infected mice. Oral infection induced the highest proportion of gamma interferon(-) CD107a/b(+) CD8 T cells in Peyer's patches. When equal numbers of rotavirus-specific CD8 T cells were transferred into Rag-1 knockout mice chronically infected with rotavirus, the donor cells derived from Peyer's patches of orally infected mice were more efficient than those derived from lungs of intranasally infected animals in clearing intestinal infection. These results suggest that different routes of infection induce virus-specific CD8 T cells with distinct homing phenotypes and effector functions as well as variable abilities to clear infection.
CD8 T细胞应答为抵抗轮状病毒提供了重要防御，轮状病毒除感染肠道外还会感染多种全身部位。在此，我们研究了经鼻内、口服或肌肉注射途径引发轮状病毒感染后，多个器官中轮状病毒特异性CD8 T细胞的分布、表型和功能。在口服感染小鼠的派尔集合淋巴结以及鼻内感染动物的肺中观察到病毒特异性CD8 T细胞的最高水平。无论感染途径如何，在外周血或脾脏中检测到的病毒特异性CD8 T细胞水平都非常低。来自口服感染小鼠派尔集合淋巴结的轮状病毒特异性CD8 T细胞高表达CCR9，而CXCR6和LFA-1表达与鼻内感染小鼠肺中的病毒特异性CD8 T细胞相关。口服感染在派尔集合淋巴结中诱导出最高比例的γ干扰素（-）CD107a/b（+）CD8 T细胞。当将等量的轮状病毒特异性CD8 T细胞转移到慢性感染轮状病毒的Rag-1基因敲除小鼠中时，源自口服感染小鼠派尔集合淋巴结的供体细胞在清除肠道感染方面比源自鼻内感染动物肺的供体细胞更有效。这些结果表明，不同的感染途径诱导出具有不同归巢表型和效应功能以及不同清除感染能力的病毒特异性CD8 T细胞。
