Quantifying T Lymphocyte Turnover

Peripheral T cell populations are maintained by production of naive T cells in the thymus, clonal expansion of activated cells, cellular self-renewal (or homeostatic proliferation), and density dependent cell life spans. A variety of experimental techniques have been employed to quantify the relative contributions of these processes. In modern studies lymphocytes are typically labeled with 5-bromo-2’-deoxyuridine (BrdU), or with deuterium. Proper interpretation of such data in terms of the underlying rates of T cell production, division, and death has proven to be notoriously difficult and involves mathematical modeling. Unfortunately, the assumptions underlying our mathematical models may influence the interpretation our data. I will review the various models that have been developed for each of these techniques, discuss which models seem most appropriate for what type of data, and reveal open problems that require better models. Various successful cases where modeling has delivered new insights in T cell population dynamics will be discussed.