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

• Published in: The Journal of immunology (1950) Vol. 171; no. 3; pp. 1128 - 1132
• Main Authors: Faroudi, Mustapha, Zaru, Rossana, Paulet, Pierre, Muller, Sabina, Valitutti, Salvatore
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-08-2003
• Subjects: Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; Cell Communication - immunology; Cell Line, Transformed; Clone Cells; Enzyme Inhibitors - pharmacology; Flow Cytometry; Humans; Interferon-gamma - biosynthesis; Lymphocyte Activation - immunology; Pyrimidines - pharmacology; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - physiology; Signal Transduction - immunology; src-Family Kinases - antagonists & inhibitors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.3.1128

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.