Dendritic cells and control of T cell immune responses
DCs are unique antigen-presenting cells that can initiate (prime) CD4 T cell responses, as well as controlling the progression and subsequent reduction of the immune response, development of immunologic memory and activation of other cell types such as macrophages and B cells.
The interaction between dendritic cells (DCs) and CD4 T cells lies at the heart of the immune response. Although many different DC subsets and activation states have been defined, we do not yet understand the particular role of each subset, nor how they interact in vivo. In vitro analysis, while helpful in defining the ability of DCs to activate T cells, cannot accurately reproduce many of the different functional states achieved by CD4 T cells (such as deletion, anergy, suppression, effector and central memory). Our laboratory has developed a set of unique transgenic mouse models that allows us to test the outcomes of interaction between CD4 T cells and defined subsets of DCs in vivo. In these models, we restrict antigen presentation to particular DCs by restricting expression of antigen-binding MHC class II molecules. In addition, we have expressed our model antigen in a number of forms with different immunological effects: as a self-antigen (leading to deletion or differentiation of specific regulatory T cells), as part of a soluble fusion protein, used to induce tolerance, allergy, or memory, depending on how it is administered, and as part of Mycobacterium tuberculosis, a pathogenic organism that is a major cause of human infection. By testing each type of antigen with each subset of DCs, we are building a picture of how the range of CD4 T cell responses is controlled. Using these models, we have been able to show that some DC subsets are able to induce T cell proliferation without supporting the generation of memory T cells, whereas others support memory development. In addition, we have defined different responses of DC subsets to in vivo stimuli such as contact with microbes.
- Flow cytometry (FACS) - the Centenary Institute has a world-class flow cytomety facility with over $3M of sorting and analysis equipment. We routinely perform 8-9 colour sorting and analysis.
- Intravital microscopy - the Centenary Institute is purchasing a state-of-the-art 2-photon intravital microscope in mid 2007
- Confocal microscopy - the Centenary Institute is purchasing a state-of-the-art confocal microscope in mid 2007
- Transgenic and knockout mice - the Centenary Institute has an outstanding track record of making and using genetically manipulated mouse strains. The on-site animal facility is an Australian leader in mouse husbandry and complex breeding.
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The opportunity ID for this research opportunity is: 216
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