Mission Statement Graduate Student Information Contact Information MURI-2001 University of Maryland Institute for Research in Electronics and Applied Physics
Institute for Research in Electronics and Applied Physics

A joint Institute of the
College of Computer, Mathematical and
Physical Sciences
and the A. James Clark School of Engineering

Applied Dynamics Seminar

Thursday, September 24, 2009 -- 12:00 p.m.
Large Conference Room (1207), Energy Research Facility

"How Is the Primary T Cell Response Regulated?"
by
Doron Levy
Department of Mathematics and CSCAMM
University of Maryland

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.