Cutting edge: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling.
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.
Faroudi
Mustapha
M
Institut National de la Santé et de la Recherche Médicale Unité 563, Lymphocyte Interaction Group, Institut Claude de Préval, Toulouse, France.
Zaru
Rossana
R
Paulet
Pierre
P
Müller
Sabina
S
Valitutti
Salvatore
S
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D011743:Pyrimidines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C412373:AG 1879; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D019061:src-Family Kinases