Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2012 May 15;109(20):7823-8. doi: 10.1073/pnas.1205850109. Epub 2012 May 1.
Fibroblastic reticular cells (FRCs) are lymphoid stromal cells essential to T-cell migration and survival. Although FRCs are targets of multiple viral infections, little is known about their role during infection due to the cells' scarcity and difficulty in isolating in vivo. To initiate studies of interactions among FRCs, viruses, and immune cells, we isolated and immortalized CD45(-)gp38(+)CD35(-)CD31(-)CD44(+)VCAM1(+) cell lines from C57BL/6 mice designated as immortalized FRC. Using these cloned cell lines, we have established that FRCs express the major histocompatibility complex (MHC) II molecule, a factor necessary for stimulation of CD4(+) T cells thought to be expressed primarily by antigen-presenting cells, along with other T-cell stimulatory ligands in an IFN-γ-dependent manner. In this environment, lymphocytic choriomeningitis virus (LCMV)-infected iFRCs activated naive LCMV-specific CD4(+) and CD8(+) T cells while limiting expansion of effector LCMV-specific T cells. Thus, FRCs effectively presented antigen along with activating signals during viral infection using both MHC I and MHC II molecules, illustrating a previously undescribed interaction with CD4(+) T cells and indicating a unique role for FRCs.
纤维母细胞网状细胞 (FRC) 是淋巴样基质细胞，对于 T 细胞的迁移和存活至关重要。尽管 FRC 是多种病毒感染的靶标，但由于细胞数量稀少且难以在体内分离，因此对其在感染过程中的作用知之甚少。为了开始研究 FRC、病毒和免疫细胞之间的相互作用，我们从 C57BL/6 小鼠中分离并永生化了 CD45(-)gp38(+)CD35(-)CD31(-)CD44(+)VCAM1(+)细胞系，这些细胞系被命名为永生化 FRC。使用这些克隆的细胞系，我们已经确定 FRC 表达主要组织相容性复合体 (MHC) II 分子，这是刺激 CD4(+)T 细胞所必需的因素，而 CD4(+)T 细胞被认为主要由抗原呈递细胞表达，同时还以 IFN-γ 依赖的方式表达其他 T 细胞刺激配体。在这种环境下，淋巴细胞性脉络丛脑膜炎病毒 (LCMV) 感染的 iFRC 激活了幼稚的 LCMV 特异性 CD4(+)和 CD8(+)T 细胞，同时限制了效应性 LCMV 特异性 T 细胞的扩增。因此，FRC 在病毒感染期间使用 MHC I 和 MHC II 分子有效呈递抗原和激活信号，这表明与 CD4(+)T 细胞之间存在以前未描述的相互作用，并表明 FRC 具有独特的作用。
