| First Author | Marchingo JM | Year | 2014 |
| Journal | Science | Volume | 346 |
| Issue | 6213 | Pages | 1123-7 |
| PubMed ID | 25430770 | Mgi Jnum | J:259318 |
| Mgi Id | MGI:6147884 | Doi | 10.1126/science.1260044 |
| Citation | Marchingo JM, et al. (2014) T cell signaling. Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion. Science 346(6213):1123-7 |
| abstractText | 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. |
