Program
| MSC6d | |
|---|---|
| Vitaly Ganusov | |
| Los Alamos National Laboratory | |
| Title | The contribution of cell-intrinsic vs. extrinsic factors in determining magnitude of expansion of CD4 T cell populations |
| Abstract | It is generally accepted in immunology that after initial activation CD8 and CD4 T cells undergo programmed proliferation and differentiation into effectors. What controls expansion of T cell populations and what constitutes the “program” of the T cell response remains poorly understood. Broadly speaking, proliferation of T cells after initial triggering could be controlled by extra-cellular (e.g., level of antigen, cytokines, other cells, etc.) or intra-cellular (e.g., number of cell division) factors. Using a system of in vitro stimulated CD4 T cells, we investigated how the concentration of interleukin 2 (IL-2), a known “growth” factor of T cells, controls the magnitude of expansion of T cells in vitro. Specifically, we analyze data on the dynamics of CFSE-labeled polyclonal CD4+ T lymphocytes in vitro after anti-CD3 stimulation at different concentrations of exogenous IL-2. We find that to adequately describe the dynamics of T cells at low concentrations of exogenous IL-2, the death rate of divided cells has to increase with the number of divisions, cells have undergone. IL-2 hardly affects the average interdivision time. At low IL-2 concentrations 1) fewer cells are recruited into the response and successfully complete their first division; 2) the stochasticity of cell division is increased; and 3) the rate, at which the death rate increases with the division number, increases. In contrast, the model in which division and death rates of T cells depend on the IL-2 concentration, failed to adequately describe these data and also generated predictions that were inconsistent with additional measurements. In summary, our results suggest that expansion of CD4 T cell populations, at least in vitro, could be controlled by cell intrinsic factors. |
| Location | Woodward 6 |