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J Immunol. 2003 Aug 1;171(3):1128-32.

Cutting edge: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling.

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  • 1Institut 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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