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A new publication by PhD student Nicolas Jaccard
Dr. Irenjeet Bains
For my PhD, I worked on modelling T cell dynamics in HIV. T cell homeostasis describes the process through which the immune system regulates cell survival, proliferation, differentiation and death to maintain T cell numbers and diversity in a range of different conditions. Understanding T cell homeostasis requires knowledge of the export rate of new T cells from the thymus, a rate that has been surprisingly difficult to estimate. The aim of my work was to better understand how this process leads to the development of the naive CD4+ T cell compartment during childhood.
Mathematical modelling was used in combination with experimental observations to estimate naive T cell kinetics over the lifetime of an individual. My analysis showed that post-thymic proliferation contributes more than double the number of cells entering the pool each day from the thymus. This ratio is preserved from birth to age 20 years; as the thymus involutes, the average time between naive T cell divisions in the periphery lengthens with age and the naive population is maintained by improved naive cell survival. TCR excision circle (TREC) content has been used as a proxy for thymic export, but this quantity is influenced by cell division and loss of naive T cells and is not a direct measure of thymic export.
I developed a method for quantifying thymic export in humans by combining two simple mathematical models. One uses Ki67 data to calculate the rate of peripheral naive T cell production, whereas the other tracks the dynamics of TRECs. Combining these models allows the contributions of the thymus and cell division to the daily production rate of T cells to be disentangled. I also explored the role of inter-cellular variation in T cell residency times. My model is able to explain the persistence of PTK7+ naive T cells, so called recent thymic emigrants, in thymectomised individuals.The model has implications for the use of PTK7 as a marker of recent thymic emigration and also naturally explains improved T cell survival in older individuals.
I am going on to do a postdoc in theoretical immunology in the Yates Lab, Albert Einstein College of Medicine.
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