RegenerativeMedicine.net

Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion

Authors: Julia M. Marchingo, Andrey Kan, Robyn M. Sutherland, Ken R. Duffy, Cameron J. Wellard, Gabrielle T. Belz, Andrew M. Lew, Mark R. Dowling, Susanne Heinzel, & Philip D. Hodgkin

Summary:

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.

Source: Science; Vol. 346, No. 6213, 1123-1127 (11/28/14)