Autoimmunity and Transplantation

Research Focus

Overview

Each of us relies on the immune system to guard the body against invasion by harmful agents. Having the immune system recognise and maintain the distinction between “self” and potentially harmful “non-self” is crucial in the avoidance of autoimmune diseases. Autoimmune disease results from a breakdown of the immune system’s ability to discriminate between “self” and “non-self”. This breakdown can cause diseases such as type 1 diabetes, rheumatoid arthritis and coeliac disease. These diseases share a common theme of misdirected immune responses in genetically susceptible individuals, causing damage to target tissues: the insulin-producing beta cells of the pancreas in type 1 diabetes; the joints in rheumatoid arthritis; and the small intestine in coeliac disease.

In our Division, we seek to better understand these common autoimmune diseases in order to improve current diagnosis and treatment and devise means for their prevention. We employ the spectrum of biomedical research strategies, from mouse models of human disease through to the analysis of cells, proteins and DNA from patients and families. This comprehensive approach is facilitated by strong linkages to clinical services at Melbourne Health, where three of our laboratory heads have concurrent clinical appointments.

This year, we highlight our recent work on regulatory T cells, which represent an important mechanism for keeping the immune system in check. These cells, identified in human subjects, express a novel surface marker and respond specifically to antigens found in the beta cells of the pancreas. Deficiency of these regulatory cells could contribute to type 1 diabetes and boosting them could help treat and even prevent the disease.

We study fundamental immune mechanisms that may help understand human disease. We highlight an Achilles’ heel in the generation of killer T cells, which may have important therapeutic potential in reducing transplant rejection. Our studies of key cytokine mediators in rheumatoid arthritis progresses, with further findings on the disease-promoting role of G-CSF and with biotechnology collaborations to develop G-CSF antagonists for clinical trials. The antigens that drive coeliac disease have now been mapped in great detail and this work provides a foundation for designing vaccines to divert the immune response. A large, multi-centre trial of intranasal insulin vaccine for the prevention of type 1 diabetes is underway, and planning for the first trial of a peptide vaccine for coeliac disease is well advanced.