Lin Wei, Suo Yuanzhen, Deng Yuting, Fan Zhichao, Zheng Yijie, Wei Xunbin, Chu Yiwei
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Biotherapy Research Centre, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
BMC Immunol. 2015 Aug 26;16:49. doi: 10.1186/s12865-015-0108-x.
The changes in T-cell morphology during immunological synapse (IS) formation are essential for T-cell activation. Previous researches have shown that T cell changed from spherical to elongated and/or flattened during in contact with B cell. As most powerful antigen presenting cell, dendritic cell (DC) has a strong ability to activate T cells. However, the morphological change of T cell which contacts DC and the relationship between morphological change and T-cell activation are not very clear. Thus, we studied the morphological change of CD4(+) T cell during contact with DC.
Using live-cell imaging, we discovered diversity in the T-cell morphological changes during contact with DCs. The elongation-flattening of CD4(+) T cells correlated with a low-level Ca(2+) response and a loss of T-cell receptor (TCR) signalling molecules in the IS, including zeta-chain associated protein kinase 70 (ZAP-70), phospholipase C-γ (PLC-γ) and protein kinase C-θ (PKC-θ), whereas rounding-flattening correlated with sufficient CD4(+) T-cell activation. Different morphological changes were correlated with the different amount of accumulated filamentous actin (F-actin) in the IS. Disruption of F-actin by cytochalasin D impaired the morphological change and the localisation of calcium microdomains in the IS and decreased the calcium response in CD4(+) T cells.
Our study discovered the diversity in morphological change of T cells during contacted with DCs. During this process, the different morphological changes of T cells modulate T-cell activation by the different amount of F-actin accumulation in the IS, which controls the distribution of calcium microdomains to affect T-cell activation.
免疫突触(IS)形成过程中T细胞形态的变化对于T细胞激活至关重要。先前的研究表明,T细胞在与B细胞接触时会从球形变为细长形和/或扁平形。作为最强大的抗原呈递细胞,树突状细胞(DC)具有很强的激活T细胞的能力。然而,与DC接触的T细胞的形态变化以及形态变化与T细胞激活之间的关系尚不清楚。因此,我们研究了CD4(+) T细胞与DC接触过程中的形态变化。
使用活细胞成像技术,我们发现T细胞与DC接触过程中形态变化具有多样性。CD4(+) T细胞的伸长-扁平与低水平的Ca(2+)反应以及IS中T细胞受体(TCR)信号分子的丢失相关,这些信号分子包括ζ链相关蛋白激酶70(ZAP-70)、磷脂酶C-γ(PLC-γ)和蛋白激酶C-θ(PKC-θ),而圆形-扁平则与CD4(+) T细胞的充分激活相关。不同的形态变化与IS中积累的丝状肌动蛋白(F-肌动蛋白)的不同量相关。细胞松弛素D破坏F-肌动蛋白会损害IS中的形态变化和钙微区的定位,并降低CD4(+) T细胞中的钙反应。
我们的研究发现了T细胞与DC接触过程中形态变化的多样性。在此过程中,T细胞的不同形态变化通过IS中不同量的F-肌动蛋白积累来调节T细胞激活,F-肌动蛋白积累控制钙微区的分布以影响T细胞激活。