Immunological aspects of migration and tolerance

Abstract: The actions of the immune system are highly dependent on locality for development, memory imprinting, surveillance and effector functions. Migratory processes are therefore essential for maintaining immunological integrity of multicellular organisms. Given this complexity, it is perhaps not surprising that some of the functions employed by the immune system also are found in various other situations where a need for cellular motility is required such and angiogenesis and organogenesis. To examine the complexity and distribution migratory markers we employed a hypothesis generating approach by investigating levels of chemokine receptors in different immune cell subsets in various tissues (Paper I and II). In order to evaluate how these markers change during development we focused our attention on bone marrow derived cells and compared them with mature leukocytes in bone marrow and peripheral blood. We were able to determine how different migratory markers change with increasing cellular maturity and were also able to determine differences between different patient groups. We also addressed the expression of transcription factor Aire in bone marrow from both mice and humans (Paper III). In a series of experiments we examined expression pattern and regulation of genes related to Aire expression. We found that the transcription of Aire is present in peripheral dendritic cells in mice and down regulated in response to IFN-γ stimulation. We also demonstrated how Aire-/- KO mice have an altered composition of peripheral myeloid cells. Finally, we investigated how IgE antibodies towards a carbohydrate epitope αGal arise in both patients with cat allergy and patients with macroparasitic infections (Paper IV). We showed how the two patient groups differ in serological profile and how such serological testing can be improved by using component based antigen techniques. In summary, the thesis aims to contribute to how migratory capacity is altered with development and disease state by a combination of different laboratory and analytical techniques.