T cell signaling. Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion
- Author(s)
- Marchingo, JM; Kan, A; Sutherland, RM; Duffy, KR; Wellard, CJ; Belz, GT; Lew, AM; Dowling, MR; Heinzel, S; Hodgkin, PD;
- Details
- Publication Year 2014-11-28,Volume 346,Issue #6213,Page 1123-7
- Journal Title
- Science
- Publication Type
- Journal Article
- 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.
- Publisher
- AAAS
- Research Division(s)
- Molecular Immunology; Immunology
- PubMed ID
- 25430770
- Publisher's Version
- https://doi.org/10.1126/science.1260044
- NHMRC Grants
- NHMRC/1010654, NHMRC/1043414, NHMRC/1054925, NHMRC/1037321,
- Terms of Use/Rights Notice
- Copyright © 2014, American Association for the Advancement of Science.
Creation Date: 2014-12-02 09:02:14
Last Modified: 2015-07-16 09:41:09