RRC ID 31872
Author Marchingo JM, Kan A, Sutherland RM, Duffy KR, Wellard CJ, Belz GT, Lew AM, Dowling MR, Heinzel S, Hodgkin PD.
Title T cell signaling. Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion.
Journal Science
Abstract T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.
Volume 346(6213)
Pages 1123-7
Published 2014-11-28
DOI 10.1126/science.1260044
PII 346/6213/1123
PMID 25430770
MeSH Animals Antigens / immunology* CD8-Positive T-Lymphocytes / cytology CD8-Positive T-Lymphocytes / immunology* Cell Division Cell Proliferation Cytokines / immunology* Immune Tolerance* Lymphocyte Activation Mice Receptors, Antigen, T-Cell / immunology* Signal Transduction
IF 41.846
Times Cited 102
Mice RBRC02705 RBRC02709