Overview of Project

The long term aim of our group is to understand how the immune system chooses the appropriate response to mount under each different circumstance. This choice involves interactions between dendritic cells and T cells, which are the focus of our lab. A multitude of diseases, generally grouped under the heading autoimmune diseases, result from inappropriate immune responses. These include juvenile diabetes, rheumatoid arthritis, thyroid disease, multiple sclerosis, Crohn’s disease and ulcerative colitis. Current treatments are only partially effective and have very significant side effects. Our aim is to prevent such diseases and/or to cure them, rather than providing long term treatments that do not effectively treat the underlying condition.

We have recently discovered that one of the ways regulatory T cells prevent autoimmune disease is by controlling the expression of costimulatory molecules on dendritic cells. This led us to test whether patients with inflammatory bowel disease had deficiencies in regulatory T cell numbers that could have made them susceptible to disease. Our recent data has shown for the first time that this is indeed the case. In several other autoimmune diseases, the function of regulatory T cells may also be defective. We would like to test this in our cohort of patients with Crohn’s disease and ulcerative colitis.

Project Outline

Peripheral blood, lymph nodes and mucosa from bowel biopsies are available from patients with inflammatory bowel disease who attend the clinics of Prof Warwick Selby and Prof Michael Solomon at Royal Prince Alfred Hospital. The project will address the following questions:

1) Do regulatory T cells from patients suppress as effectively as those from normal controls?

2) What are the molecules used by regulatory T cells to control the function of dendritic cells? We are currently performing gene chip analysis which is providing an array of candidate molecules for testing in biochemical and functional assays. Regulatory T cells also produce a number of soluble molecules that affect dendritic cell function and assays will be set up to measure production of these molecules by regulatory T cells from patients and controls.

Techniques

This project will give the student experience in lymphocyte purification and labelling, tissue culture, flow cytometry, DNA microarrays, bioinformatics, RT-PCR.