Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses.
A longstanding paradox in the activation of cytotoxic T lymphocytes (CTL) arises from the observation that CTL recognize and rapidly destroy target cells with exquisite sensitivity despite the fact that cytokine production requires sustained signaling at the immunological synapse. Here we solve this paradox by showing that CTL establish sustained synapses with targets offering strong antigenic stimuli and that these synapses persist after target cell death. Simultaneously, CTL polarize lytic granules toward different cells without discrimination regarding antigenic potential. Our results show that spatiotemporal uncoupling of immunological synapse and lytic granule secretion allows multiple killing and sustained signaling by individual CTL. This unique mechanism of responding to multiple contacts provides remarkable efficiency to CTL function.
Wiedemann
Aurelie
A
Lymphocyte Interaction Group, Institut National de la Santé et de la Recherche Médicale, Unité 563, Institut Claude de Préval, 31059 Toulouse, France.
Depoil
David
D
Faroudi
Mustapha
M
Valitutti
Salvatore
S
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013569:Synapses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D011948:Receptors, Antigen, T-Cell; D002118:Calcium