Journal of Innovative Optical Health Sciences, 2018, 11 (2): 1750015, Published Online: Sep. 18, 2018  

ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells

Author Affiliations
1 Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
2 Department of Immunology and Key Laboratory of Medical Molecular, Virology of MOE/MOH, School of Basic Medical Sciences, and Biotherapy Research Centre, Fudan University, Shanghai 200032, P.R. China
3 Shandong Academy of Medical Sciences, Jinan 250030, P.R. China
Abstract
T-cell activation requires the formation of the immunological synapse (IS) between a T-cell and an antigen-presenting cell (APC) to control the development of the adaptive immune response. However, calcium release, an initial signal of T-cell activation, has been found to occur before IS formation. The mechanism for triggering the calcium signaling and relationship between calcium release and IS formation remains unclear. Herein, using live-cell imaging, we found that intercellular adhesion molecule 1 (ICAM-1), an essential molecule for IS formation, accumulated and then was depleted at the center of the synapse before complete IS formation. During the process of ICAM-1 depletion, calcium was released. If ICAM-1 failed to be depleted from the center of the synapse, the sustained calcium signaling could not be induced. Moreover, depletion of ICAM-1 in ISs preferentially occurred with the contact of antigen-specific T-cells and dendritic cells (DCs). Blocking the binding of ICAM-1 and lymphocyte function-associated antigen 1 (LFA-1), ICAM-1 failed to deplete at the center of the synapse, and calcium release in T-cells decreased. In studying the mechanism of how the depletion of ICAM-1 could influence calciumrelease in T-cells, we found that the movement of ICAM-1 was associated with the localization of LFA-1 in the IS, which affected the localization of calcium microdomains, ORAI1 and mitochondria in IS. Therefore, the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sustained calcium release in T-cells.

Yuanzhen Suo, Wei Lin, Yuting Deng, Zhichao Fan, Lizeng Qin, Guosheng Jiang, Yiwei Chu, Xunbin Wei. ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells[J]. Journal of Innovative Optical Health Sciences, 2018, 11(2): 1750015.

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