The study of T cell differentiation and function using DNA microarrays

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The immune system uses specialized cells to combat various infectious agents, such as viruses or large parasites. The immune system remembers such pathogens, and is able to mount an enhanced and more rapid response upon secondary encounter. This property, termed immunological memory, is the basis of vaccination. Sometimes the normal functioning of the immune system goes awry, producing allergic disease (such as asthma) or autoimmune diseases (such as Multiple sclerosis and possibly rheumatoid arthritis). The nature of the cells that mediate immunological memory, or the processes that lead to inflammatory disease are poorly understood. A new approach towards understanding the function and inter-relationships of T cells is to use genomics techniques, that enable tens of thousands of genes to be assessed for their expression in different cells or tissues. An understanding of which genes are inappropriately turned on in different disease states should provide new understanding of disease process, and new targets for pharmaceutical intervention. We will systematically assess gene expression in various subsets of T cells, which have known functions. For instance Th1 cells have been implicated in the pathogenesis of autoimmune disease, and Th2 cells in the pathogenesis of asthma. How these cells regulate gene expression during their differentiation, and use their newly expressed genes for their specific functions is one aim of this study. Another important subdivision of the immune system is between skin homing and gut homing T cells. Gut homing T cells are thought to mediate protection in the gut against gut pathogens, but also to cause diseases such as inflammatory bowel disease (Ulcerative colitis, Crohn's disease). Finally, understanding which cells harbour immunological memory, and how this might be manipulated to improve immune resposes, is of great importance for vaccination programs.