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

M Faroudi, R Zaru, P Paulet, S Müller… - The Journal of …, 2003 - journals.aai.org
M Faroudi, R Zaru, P Paulet, S Müller, S Valitutti
The Journal of Immunology, 2003journals.aai.org
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 …
Abstract
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-γ production and the amount of IFN-γ 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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