Morphological change of CD4+ T cell during contact with DC modulates T-cell activation by accumulation of F-actin in the immunology synapse

Abstract

Background: 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. Results: 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 Ca2+ 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. Conclusion: 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.