Liu Luzheng, Fuhlbrigge Robert C, Karibian Kara, Tian Tian, Kupper Thomas S
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Immunity. 2006 Sep;25(3):511-20. doi: 10.1016/j.immuni.2006.06.019.
After viral infection, activated T cells are present in multiple tissues regardless of the infection route. How these cells acquire pleiotropic homing ability is unclear. By using a cutaneous vaccinia virus infection model, we demonstrate that regulation of T cell trafficking is multiphasic. Upon completion of three cell divisions, CD8+ T cells upregulated specific skin-homing molecules within draining lymph nodes (LN). By 60 hr after infection, some activated T cells reached the infected tissue, while others entered distant antigen-free LN. These latter cells continued to divide and acquire additional tissue-homing molecules in this new setting, independent of antigen presentation. After viral clearance, the initial skin-homing imprint became the predominant homing phenotype on memory cells and provided superior protection against secondary cutaneous challenge. These observations demonstrate a mechanism by which T cells provide both immediate tissue-specific immune control at the pathogen entry site and a more flexible systemic protection against pathogen dissemination.
病毒感染后，无论感染途径如何，活化的T细胞都会出现在多个组织中。这些细胞如何获得多向归巢能力尚不清楚。通过使用皮肤痘苗病毒感染模型，我们证明T细胞迁移的调控是多阶段的。在完成三次细胞分裂后，CD8+T细胞在引流淋巴结（LN）内上调特定的皮肤归巢分子。感染后60小时，一些活化的T细胞到达感染组织，而另一些则进入远处无抗原的淋巴结。这些后期细胞继续分裂，并在这个新环境中获得额外的组织归巢分子，与抗原呈递无关。病毒清除后，最初的皮肤归巢印记成为记忆细胞上的主要归巢表型，并为抵御二次皮肤攻击提供了更好的保护。这些观察结果证明了一种机制，通过该机制T细胞既能在病原体进入部位提供即时的组织特异性免疫控制，又能提供更灵活的针对病原体传播的全身保护。
