| 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
|
|
WOS Category
|
IMMUNOLOGY
|
| Resource |
| Mice |
RBRC02705
RBRC02709 |
