Dendritic Cell-mediated Induction Of T Cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Australia has some of the highest rates of immune-mediated diseases in the world. These diseases include autoimmune, allergic and inflammatory conditions. We will use a mouse model to study how dendritic cells can prevent the onset of these conditions by inactivating the immune cells that cause them. Our findings will aid in understanding why these diseases develop and how they may be prevented and treated.
Mechanisms Of Rapid Memory CD8+ T-cell Inactivation
Funder
National Health and Medical Research Council
Funding Amount
$318,517.00
Summary
Type 1 diabetes (T1D) and other autoimmune diseases results from misdirected immune responses that destroy normal body tissues. The ultimate goal of therapeutic strategies is to remove or inactivate the immune cells that attack normal tissues, while leaving other immune cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off inappropriate immune reactions.
The Molecular Identification Of FoxP3 +ve Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$483,273.00
Summary
The immune system has a series of checks and balances in place to distinguish foreign bodies from normal, or self-antigens. In healthy individuals this prevents the immune system from attacking the cells and tissues of the body, food proteins, and the beneficial bacteria of the gut. However in autoimmune disease the system becomes imbalanced, allowing reactions to benign antigens, causing diseases such as diabetes, asthma and rheumatoid arthritis. One of the key players in the maintenance of a h ....The immune system has a series of checks and balances in place to distinguish foreign bodies from normal, or self-antigens. In healthy individuals this prevents the immune system from attacking the cells and tissues of the body, food proteins, and the beneficial bacteria of the gut. However in autoimmune disease the system becomes imbalanced, allowing reactions to benign antigens, causing diseases such as diabetes, asthma and rheumatoid arthritis. One of the key players in the maintenance of a healthy immune system is a specialized set of T cells known as T Regulatory cells. These cells are rare, at 1-4% of all T cells, yet are potent modulators of other T cells, and can prevent the activation of a T cell if it is reacting to a self-antigen. If they can control the cause of autoimmune disease, and patient Treg cells can be manipulated, it may be possible to use them therapeutically. Recently the switch that is required to generate regulatory cells was identified from patients with a rare autoimmune disease called Immunodysregulation, polyendocrynopathy, enteropathy, X-linked syndrome or IPEX. A mouse disease, Scurfy, with similar symptoms, is caused by the same mutations. The mutated gene encodes a protein, FoxP3, and this protein is able to bind to other genes in T cells and regulate their function. Without this protein, there are no T regulatory cells, resulting in autoimmune disorders. At this time there is very little known about how the FoxP3 gene is able to make a T cell become a regulatory T cell, and nothing is known about the genes that are turned off and on to facilitate this. If we can understand better the role of this protein, FoxP3, in the generation and maintenance of T cells with regulatory function, we may better be able to diagnose and treat autoimmune diseases, and this knowledge will have broad application to many autoimmune disorders.Read moreRead less
Our research has identified unprecedented communications between the microbes that colonize our body’s surfaces and killer T cell immunity. Our findings indicate that microflora is key to a healthy balance between two immune mediator systems that have opposing effect on T cell immunity. The project will extend our understanding of how this regulated and seeks to harness these novel insights to explain the well known, but poorly understood role of microbes in autoimmune diseases.
Mechanisms Of Dendritic Cell-induced T-cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to using the cells which train the immune system to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. Thes ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic suceptibility to autoimmune disease, the mechanisms fail and the body's immune sytem attacks normal tissues or organs. We have developed a new approach to using the cells which train the immune system to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project we will explore how these cells can be used to turn off cells of the immune system and if cells of the immune system in turn control the dendritic cell's ability to do this.Read moreRead less
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. The ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project, we will explore how these cells can be used to turn off the harmful cells present in the immune system.Read moreRead less