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The Journal of Immunology, 2003, 171: 1128-1132.
Copyright © 2003 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: T Lymphocyte Activation by Repeated Immunological Synapse Formation and Intermittent Signaling 1

Mustapha Faroudi, Rossana Zaru, Pierre Paulet, Sabina Müller and Salvatore Valitutti2

Institut National de la Santé et de la Recherche Médicale Unité 563, Lymphocyte Interaction Group, Institut Claude de Préval, Toulouse, France

The activation of biological T cell responses requires prolonged contact with APCs and sustained signaling. We investigated whether signaling must be uninterrupted to commit T cells to cytokine production or whether T cell activation may also result from summation of interrupted signals. Upon periodic addition and removal of a src kinase inhibitor, human CD4+ T cells destroyed and re-formed immunological synapses while aborting and restarting signal transduction. Remarkably, under these conditions, T cells were eventually activated to IFN-{gamma} production and the amount of IFN-{gamma} produced was directly related to the total signaling time despite the repeated interruptions. Our results illustrate that T cell activation does not require a stable immunological synapse and can be achieved by interrupted signaling. It is implied that T cells can add activation signals, possibly collected on multiple APCs.




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