A joint Institute of the College of Computer, Mathematical and Physical Sciences and the A. James Clark School of Engineering |
The currently accepted paradigm for the primary T cell response is that effector T cells commit to autonomous developmental programs. This paradigm is based on experiments that study the dynamics of T cell responses over a wide variety of stimulation levels and initial conditions. This work studies the hypothesis that the dynamics of a primary response is governed by adaptive regulatory cells rather than by intrinsic developmental programs. We formulate two mathematical models based on developmental programs. In one model, effector cells may undergo a fixed number of divisions before dying. In the second model, effector cells live for a fixed time during which they may divide. The study of these models suggests that developmental programs are not robust as they produce an immune response that scales with precursor frequencies. Consequently, we derive a third model based on the principle that adaptive regulatory T cells develop in the course of an immune response and suppress effector cells. Our simulations show that this feedback mechanism responds robustly over a range of at least four orders of magnitude of precursor frequencies. We conclude that the proliferation program paradigm is either incomplete or incorrect. We propose a mechanism by which the primary T cell response is governed by an emergent group dynamic and not by individual T cell programs.