Quantification of T-cell dynamics: from telomeres to DNA labeling

Immunology has traditionally been a qualitative science describing the cellular and molecular components of the immune system and their functions. Only quite recently have new experimental techniques paved the way for a more quantitative approach of immunology. Lymphocyte telomere lengths have been measured to get insights into the proliferation rate of different lymphocyte subsets, T-cell receptor excision circles have been used to quantify the daily output of new T cells from the thymus, and bromodeoxyuridine and stable isotope labeling have been applied to measure proliferation and death rates of naive and memory lymphocytes. A common problem of the above techniques is the translation of the resulting data into relevant parameters, such as the typical division and death rate of the different lymphocyte populations. Theoretical immunology has contributed significantly to the interpretation of such quantitative experimental data, thereby resolving diverse controversies and, most importantly, has suggested novel experiments, allowing for more conclusive and quantitative interpretations. In this article, we review a variety of different models that have been used to interpret data on lymphocyte kinetics in healthy human subjects and discuss their contributions and limitations.