School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
PLoS One. 2013;8(3):e59793. doi: 10.1371/journal.pone.0059793. Epub 2013 Mar 26.
T lymphocytes (T cells) circulate from the blood into secondary lymphoid organs for immune surveillance. In this study, we hypothesized that circulating T cells are heterogeneous and can be grouped according to their differential migratory capacity in response to chemoattractants, rather than expressions of certain receptors or cytokines. We further hypothesized that, at least in part, this intrinsic difference in motility may be related to the T cell function. We established motile (m-T) and non-motile T (nm-T) cell lines based on their response to the chemokine SDF-1α. m-T cells showed more irregular and polarized morphologies than nm-T cells did. Interestingly, m-T cells produced higher levels of IL-2, a marker for T cell activation, than nm-T cells did after stimulation; however, no differences were observed in terms of surface expression of T cell receptors (TCR), adhesion molecules LFA-1 and ICAM-1, and chemokine receptor CXCR4. Both cell lines also showed similar membrane events (i.e., T cell-APC conjugation, LFA-1 accumulation at the immunological synapse, and TCR internalization). In contrast, PKC-θ, a downstream of PI3K-Akt pathway was constitutively activated in m-T cells and the activation was more prominent during T cell stimulation. Consequently, NF-κB activity was selectively upregulated in m-T cells. This study is the first, to our knowledge, to demonstrate that T cells can be subcategorized on the basis of their intrinsic migratory capacity in relation to T cell activation.
T 淋巴细胞（T 细胞）从血液循环到次级淋巴器官进行免疫监视。在这项研究中，我们假设循环 T 细胞是异质的，可以根据它们对趋化因子的不同迁移能力进行分组，而不是根据特定受体或细胞因子的表达进行分组。我们进一步假设，至少在某种程度上，这种内在的运动能力差异可能与 T 细胞功能有关。我们根据对趋化因子 SDF-1α的反应建立了可移动（m-T）和不可移动 T（nm-T）细胞系。m-T 细胞表现出比 nm-T 细胞更不规则和极化的形态。有趣的是，m-T 细胞在刺激后产生的 IL-2 水平（T 细胞活化的标志物）高于 nm-T 细胞；然而，在 TCR、粘附分子 LFA-1 和 ICAM-1 以及趋化因子受体 CXCR4 的表面表达方面没有观察到差异。两种细胞系也显示出类似的膜事件（即 T 细胞-APC 共轭、LFA-1 在免疫突触处的积累和 TCR 内化）。相比之下，PKC-θ（PI3K-Akt 途径的下游）在 m-T 细胞中持续激活，并且在 T 细胞刺激期间激活更为明显。因此，NF-κB 活性在 m-T 细胞中被选择性地上调。据我们所知，这项研究首次证明 T 细胞可以根据与 T 细胞活化相关的内在迁移能力进行分类。
