The Role Of Aire In Immunological Tolerance And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
The immune system is designed to protect us from foreign pathogens such as bacteria, viruses and parasites. This is achieved through lymphocytes which recognise foreign pathogens. However in 5-6% of the population the immune system attacks the host and induces autoimmunity. We aim to understand the mechanisms which control the production of self-reacting lymphocytes and how we may reduce the incidence of autoimmunity.
Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Tolerogenic Dendritic Cells In Common Marmoset Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$162,756.00
Summary
ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxi ....ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxicity. TRANSPLANTS ARE REJECTED when a recipient's immune system sees the kidney as foreign. Immune suppressing drugs prevent rejection by stopping the reaction to foreign tissues, but this causes increased infection and cancer risk. IMMUNE TOLERANCE means the recipient's immune system sees a transplant not as foreign but as part of itself, no longer reacting to it. If tolerance could be achieved for transplants, patients wouldn't need to use immune suppressing drugs. Costs of immune suppression would be nil. Tolerance is the best long-term solution for patients needing transplants. Tolerance has been achieved in various ways in mice models. DENDRITIC CELLS can be used to induce tolerance as they can silence a recipient's immune system, preventing it from seeing transplant tissues as foreign. We have shown in mice that a single infusion of a certain type of dendritic cells caused prolonged transplant tolerance without needing immune suppression. This project aims to use dendritic cells to induce tolerance in a marmoset model - a required step before allowing this therapy to be done in humans. PRIMATES like MARMOSETS have close genetic identity to humans and are ideal transplant models as their immune systems react much more like humans than other animals. Marmosets are not an endangered species and are smaller, cheaper and easier to care for than other primates. Ultimately, experiments in other species would need repeating in primates before human trials could be done.Read moreRead less
Role Of Dendritic Cell Subsets In The Generation Of CD4 T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
This project studies the mechanisms responsible for establishing immunologic memory that is generated by vaccination and determines its efficacy. We aim to identify and study previously unacknowledged factors that critically affect the efficacy of vaccination. The results will be significant for both preventative and therapeutic vaccination (cancer, autoimmunity) and will help us to design new vaccines to improve immune function in infection, autoimmunity and cancer.
Understanding The Key Attributes Of CD8 T Cell Receptor Transfer As An Antiviral Strategy And Harnessing The Process To Combat Persistent Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
We have recently discovered a new process through which the numbers of antiviral immune cells can rapidly expand, without dividing, to combat a virus infection that may otherwise be fatal. This represents a significant advance in our knowledge on how a speedy, virus-specific response can be mounted. We will study how this process can be applied to therapeutic strategies to overcome medically significant persistent viral infections.
Modulation Of HIV-1 Latency In Primary CD4 T Cells By Chemokines And Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$380,167.00
Summary
Although treatment of HIV using antiretroviral drugs has dramatically improved outcome the presence of latent infection in long lived T cells has so far prevented cure of HIV infection. This study examines the roles of chemokines (proteins that control cell migration) and a special type of infection fighting cell, the dendritic cell, in generating latent infection in resting T cells. These studies could potentially identify new ways to treat and potentially cure HIV infection.
The Role Of Dendritic Cell Subsets In The Decision Between T Cell Tolerance And Immunity
Funder
National Health and Medical Research Council
Funding Amount
$445,009.00
Summary
The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing the ....The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. The question of how lymphocytes can tell the difference between the body itself and foreign organisms is of major interest to immunologists. One of the first ideas was that self-reactive lymphocytes are inactivated by making reactions early in life. Despite the simplicity and intellectual appeal of this idea, it is inconsistent with a large body of experimental evidence. On the basis of number of new experiments, I have proposed an alternative model of self tolerance for one of the subsets of lymphocytes. In this model, the cells that help lymphocytes to recognise particular substances possess the property of distinguishing self from foreign, and pass that information on. The aim of this project is to provide direct experimental evidence in support of the model. Many of our attempts to deal with medical problems related to the immune system have been hampered by our lack of understanding of exactly how immune tolerance is controlled. If my model proves to be correct, it will be possible to manipulate immune responses with far greater effectiveness, providing new treatments for autoimmune disease, allergy, graft rejection and vaccination.Read moreRead less
Tolerogenic Dendritic Cells In Kidney Transplantation: Studies In Common Marmoset Monkeys
Funder
National Health and Medical Research Council
Funding Amount
$124,014.00
Summary
Kidney transplantation is the preferred treatment for end-stage kidney disease, but requires immunosuppressive drugs to prevent transplant rejection. However, long-term immunosuppression can have toxic side effects and increase the risks of infection and cancer. This research examines the therapeutic potential of dendritic cells (a specialised immune cell-type) to promote tolerance of the transplant kidney, while enabling maintenance of normal immune function and avoidance of immunosuppression.