TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.
ONTRANS: Oral Nicotinamide For Skin Cancer Chemoprevention After Transplant
Funder
National Health and Medical Research Council
Funding Amount
$624,824.00
Summary
The skin’s immune system is a key defence against skin cancer. Transplant recipients, who are chronically and profoundly immune suppressed to prevent rejection, have a 50-80 fold increase in skin cancer risk. Nicotinamide (vitamin B3) reduced skin cancer in our recent Phase 3 trial in immune competent individuals. A pilot study in renal transplant patients showed similar results. This project will determine at the Phase 3 level whether nicotinamide reduces skin cancers after kidney transplant.
Human Cytomegalovirus Encoded Control Of The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$639,871.00
Summary
Human cytomegalovirus has the ability to hide in the body of a person throughout their life time without it making them ill but the virus can awaken (reactivate) from this latent state and produce new virus. In immunosuppressed people such as transplant patients this reactivation causes significant problems, even death, yet this latency remains poorly understood. This project will help us to understand how the virus can hide successfully from the immune system in a latent form in the human host.
Combining Immune Monitoring And Immunotherapy To Tackle Cytomegalovirus Infections In Solid Organ Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$801,416.00
Summary
Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and tr ....Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and treat these patients with killer T cells.Read moreRead less
Unraveling Mechanisms Of Liver Transplant Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$694,822.00
Summary
Liver transplants are unique amongst solid organs as they are spontaneously accepted across different individuals and induce acceptance of other organs from the same donor co-transplanted at the same time. Using a new mouse liver transplantation model, this proposal will elucidate how the liver tissue performs this function and identify new markers associated with tolerance in the blood of mice. This knowledge will be used to identify liver transplant patients with reduced rejection risk.
Tracking The Impact Of Superinfection With A Common Herpesvirus On T Cell Immunity In Humans
Funder
National Health and Medical Research Council
Funding Amount
$317,775.00
Summary
Human herpesviruses, including cytomegalovirus, infect the vast majority of people and can cause serious complications in healthy people and in immune suppressed transplant patients. The development of vaccines to treat herpesvirus infections remain a signficant priority. However it is not known what impact repeated exposure to different strains of these viriuses has upon immunity. This study will investigate the impact of exposure to different strains of cytomegalovirus on immunity in healthy i ....Human herpesviruses, including cytomegalovirus, infect the vast majority of people and can cause serious complications in healthy people and in immune suppressed transplant patients. The development of vaccines to treat herpesvirus infections remain a signficant priority. However it is not known what impact repeated exposure to different strains of these viriuses has upon immunity. This study will investigate the impact of exposure to different strains of cytomegalovirus on immunity in healthy individuals and transplant patients.Read moreRead less
Impaired Respiratory Tolerance In Obesity - The Link With Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$667,294.00
Summary
Australia has one of the highest obesity rates in the world, placing a major strain on health budgets. Obesity increases the risk of numerous diseases, including asthma. Asthma is prevented in healthy people by the immune system. This project will investigate whether obesity-related dietary factors and/or gut microbes impair this immune-mediated mechanism. Outcomes will increase understanding of the effects of diet and obesity on asthma development, and lead to novel asthma therapies.
Deciphering How TCR Affinity Regulates CD4 T Cell Help In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$850,885.00
Summary
Immune responses require the coordinated interaction and cross-talk between two types of white blood cells known as CD4 and CD8 T cells. A dysregulated interaction between these cells could be the cause of autoimmune and persistent infections by pathogens leading to chronic diseases. The aim of this proposal is to provide a deeper understanding of CD4/CD8 T cell interactions to improve immune outcomes in many chronic diseases in which interaction between these two immune cells is critical.
The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.