Guanyu Wang

A biodynamical model of human T-cell development and pathology: design, testing and validation

We describe a coupled ordinary differential equation model of human T-cell proliferative disorders based upon documented changes in various pools such as the bone marrow, thymic compartments and peripheral blood. The conceptual design of the model is based upon previously collected experimental data, its testing and validation by comparing with normal human cell pool data at various ages as well as their changes in response to HTLV-1, HHV-6 and HIV-1 viral infections. These viruses were chosen because they all target the same CD4 lymphocyte, yet produce different response patterns such as hyperplasia, aplasia and neoplasia. They were also selected because respective cell pool data were available for comparison with detailed human studies. The ultimate task of this modeling effort is to simulate the development of T-cell lymphomas and other immunoproliferative or aproliferative (i.e. aplastic) abnormalities reported in the literature.

Computational Simulation of HHV-6 Infection

Publisher Summary The variable dynamics of a cellular immune response following an acute or chronic HHV-6 infection can be well characterized by a mathematical model. Such a computational model has the advantage of reducing intractable real-world complexities to tractable mathematical problems, while upholding the realistic biological dynamics. The power of mathematical modeling is that diverse phenomena and dynamics can be studied using the same model. Different diseases can be studied under the same paradigm. The described model contributes to explaining such variable disease courses. The model is a nonlinear one, which generates different dynamical behaviors of immunocompetent T-cell populations under different parameter conditions. Clinically this implies that diverse disease outcomes can be attributed to different sets of model parameters of patients such as rate of infection, duration of exposure to the virus, intensity of immune response etc. The present model can even be used to study HIV infection, because the immune responses following HIV infection are similar to those of HHV-6 infection. The differences consist in that in HIV infection, the model uses another set of parameters, which characterize a more vicious virus.