Mechanisms of T cell recruitment in dermal inflammation
thesis
posted on 2017-01-31, 00:13authored byAbeynaike, Latasha
T cells are a vital component of the skin inflammatory response. In common inflammatory skin diseases such as dermatitis and psoriasis, the presence of T cells has been highly associated with disease. However, while most T cells are proinflammatory, a small population of T cells, known as regulatory T cells, function to regulate the inflammatory response. Studies have shown that these cells must have the capacity to home to the skin to exert their effects. The process by which these cells enter the site of inflammation from the circulation is leukocyte recruitment, and involves the steps rolling, adhesion and transendothelial migration. While these processes are well-defined for leukocytes in general, few studies have examined endogenous T cells in the microvasculature of the skin, due to the difficulty in visualising these low frequency populations. In addition, it is unknown whether the different types of T cells have different recruitment mechanisms. Similarly, the molecular basis of these interactions is poorly understood. Understanding the involvement of specific adhesion molecules in the recruitment of different T cell subsets could be the key to the development of successful novel therapies. Therefore, the aim of this project was to identify the mechanisms of recruitment of T cell subsets, particularly comparing proinflammatory T cells with anti-inflammatory regulatory T cells, during a skin inflammatory response. This project utilised the mouse contact sensitivity (CS) model and modern imaging techniques to visualise rolling, adhesion and transendothelial migration of rare, endogenous T cell subsets in the inflamed dermal microvasculature. In summary, the experiments presented in this thesis have provided novel information regarding T cell subset recruitment to the skin during contact sensitivity.