Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation

Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs an...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2011-09, Vol.187 (6), p.3121-3132
Main Authors: Mendoza-Naranjo, Ariadna, Bouma, Gerben, Pereda, Cristián, Ramírez, Marcos, Webb, Kevin F, Tittarelli, Andrés, López, Mercedes N, Kalergis, Alexis M, Thrasher, Adrian J, Becker, David L, Salazar-Onfray, Flavio
Format: Article
Language:English
Subjects:
Animals
Cell Communication - immunology
Cell Separation
Connexin 43 - immunology
Connexin 43 - metabolism
Flow Cytometry
Fluorescent Antibody Technique
Gap Junctions - immunology
Gap Junctions - metabolism
Humans
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Immunological Synapses - immunology
Immunological Synapses - metabolism
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Receptor Cross-Talk - immunology
Signal Transduction - immunology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
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Summary:Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs and stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and time dependent, and required an intact actin cytoskeleton. Fluorescence recovery after photobleaching and Cx43-specific inhibitors were used to prove that intercellular communication between T cells and dendritic cells is bidirectional and specifically mediated by Cx43. Moreover, this intercellular cross talk contributed to T cell activation as silencing of Cx43 with an antisense or inhibition of GJ docking impaired intracellular Ca(2+) responses and cytokine release by T cells. These findings identify Cx43 as an important functional component of the immunological synapse and reveal a crucial role for GJs and hemichannels as coordinators of the dendritic cell-T cell signaling machinery that regulates T cell activation.
ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.1100378