Marchingo, J.M. and Kan, A. and Sutherland, Robyn M. and Duffy, Ken R.
(2014)
Antigen affinity, costimulation, and
cytokine inputs sum linearly to
amplify T cell expansion.
Science, 346 (6213).
pp. 1123-1127.
ISSN 0036-8075
Abstract
Tcell responses are initiated by antigen and promoted by a range of costimulatory signals.
Understanding how Tcells integrate alternative signal combinations and make decisions
affecting immune response strength or tolerance poses a considerable theoretical challenge.
Here, we report that Tcell 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 Tcell 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.
| Item Type: |
Article
|
| Keywords: |
Antigen affinity; costimulation;
cytokine inputs; sum linearly;
amplify T cell expansion; |
| Academic Unit: |
Faculty of Science and Engineering > Research Institutes > Hamilton Institute |
| Item ID: |
8284 |
| Identification Number: |
https://doi.org/10.1126/science.1260044 |
| Depositing User: |
Dr Ken Duffy
|
| Date Deposited: |
08 Jun 2017 13:32 |
| Journal or Publication Title: |
Science |
| Publisher: |
American Association for the Advancement of Science |
| Refereed: |
No |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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