Treating diabetes by modulating cross presentation
Type 1 diabetes mellitus is an autoimmune disease in which insulin-producing cells (termed beta cells) in the pancreas are destroyed. We have determined that beta cell death in the pancreas allows beta cell antigens to be processed by specialized antigen presenting cells called dendritic cells. These dendritic cells can then activate diabetes-inducing cytotoxic T cells through a process termed cross-presentation. We are currently determining which additional factors are required for the detrimental cross-presentation of self-antigen and how this may be inhibited.

SLE, UV light and T cell priming in the skin
Systemic lupus erythematosus (SLE) is an autoimmune disorder that can have devastating consequences. Lupus often begins in the skin and can worsen with exposure to sunlight. Recent experimental data in mouse models suggests that the skin may be the organ where T cells are first activated in lupus. Recent data also suggest that cytotoxic T cells may be involved in the initiation of lupus autoimmunity. A better understanding of how the skin may initiate immune responses will shed light on the role of the skin in initiating and/or perpetuating disease activity in systemic lupus erythematosus.

Epicutaneous modulation of T cell function
Recent evidence suggests that proteins or peptides can be applied on intact skin to vaccinate and produce both an antibody and a T cell response. Epicutaneous immunization (that is, on intact skin) offers potential for the development of tumour and virus-specific vaccines. In addition, it may be more cost effective as well as easier to administer than current methods of immunization. We are studying the epicutaneous application of peptides and proteins and methods to enhance their delivery and immunogenicity. In addition to being an ideal organ for the initiation of immune responses, the skin can suppress immune responses. It is particularly effective in this regard after exposure to ultraviolet light. Consequently, we are also studying how the skin may be used to induce tolerance and thereby possibly treat autoimmune disease.