Carina Bruckmaier

Short description of my project:

Almost all insights into the human immune system are based on studies of cells derived from peripheral blood. Yet, the vast majority of immune cells is not recirculating through the blood, and is instead located in tissues such as bone marrow, skin and gut. As a result, it remains largely unknown how these cells maintain themselves. This has not been adequately addressed due to a lack of good methodology and the difficulty in obtaining cells from tissues. Using in vivo deuterated water labelling, we aim to study the dynamics of T cells with a focus on tissue resident memory T cells (T_RM) in human skin and bone marrow. Once available in body water, deuterium can be incorporated into the DNA of proliferating cells. As soon as deuterium is no longer available in body water and cells die, the amount of labelled DNA decreases. The expected lifespans and turnover rates of different cell populations can then be quantified based on these changes in label abundance using mathematical models.

In a parallel project we are investigating the dynamics of stem cell memory T (T_SCM) cells. It has been suggested that the T_SCM pool consists of one large proliferating subpopulation, which is in fact a transition state between naive and effector/memory cells, and another smaller subpopulation of slowly proliferating T_SCM cells, which are truly responsible for long term memory. The model is based on the assumption that there is a constant telomere length difference between naive and T_SCM cells, and would predict that the fraction dividing T_SCM cells decreases with age. To verify this model, we are investigating the telomere length of T_SCM and naive T cells, and the level of proliferation of T_SCM cells isolated from the blood of healthy participants of different ages.