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Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence ind ....Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence indicate that BAFF may be important in T cell biology. Current studies suggest that BAFF exerts a pro-inflammatory effect upon T cell responses. Surprisingly then, when we examined the role of BAFF upon T cell function in vivo in the context of the allo-immune response, we found that ~60% of BAFF transgenic mice failed to reject a fully-mismatched allograft. Intriguingly, BAFF transgenic mice exhibited an increased number of CD4+ CD25+ Foxp3+ cells in the periphery and in vivo depletion of these CD25+ cells restored the ability of BAFF transgenic mice to reject an allograft. We hypothesize that BAFF plays a potentially powerful anti-inflammatory role in regulating certain T cell dependent immune responses. Our data suggests that BAFF can modulate T cell function by effecting T cell regulation.Read moreRead less
CD39 Protects Against Renal Ischaemic-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$441,584.00
Summary
In many medical settings, such as heart attacks, strokes, transplantation, heart surgery, shock and infection, the blood supply to an organ may be compromised resulting in damage. The cessation of blood flow depletes the organ of oxygen and generates a number of toxic changes. Re-establishing blood flow to the organ is essential to prevent further damage, however the reestablishment of blood flow itself can be harmful to the organ. The return of blood flow, oxygen and energy can actually promote ....In many medical settings, such as heart attacks, strokes, transplantation, heart surgery, shock and infection, the blood supply to an organ may be compromised resulting in damage. The cessation of blood flow depletes the organ of oxygen and generates a number of toxic changes. Re-establishing blood flow to the organ is essential to prevent further damage, however the reestablishment of blood flow itself can be harmful to the organ. The return of blood flow, oxygen and energy can actually promote more widespread injury - a process known as ischaemia-reperfusion injury (IRI). A greater understanding of IRI should aid in the development of drugs that minimise its impact. The overall aim of this work is to examine the role of a molecule - CD39 - in IRI. This molecule is ideally situated to minimise injury - it is located on cells that line blood vessels and, as such, is able to directly neutralise toxins released in response to this injury. We, therefore, believe that it will be protective in this setting. We have developed animals that express this molecule and have preliminary results to suggest that these animals are protected in experimental models of IRI as well as in several other models including heart transplantation surgery; processes that share many features with IRI. Moreover, mice deplete of this molecule are prone to more severe IRI. We aim to investigate this by using animals both lacking and expressing CD39. Blood flow to the kidneys will be interrupted for 30 minutes and kidney function assessed at 24 and 48 hours. We will then delve into the potential mechanisms underpinning IRI by determining whether the kidney itself or the blood cells afford protection, which has direct clinical implications.Read moreRead less
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
Prophylactic Vaccine To Prevent Cytomegalovirus Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,360.00
Summary
This project is aiming to develop a prophylactic vaccine against a common herpesvirus which has been linked to the birth defects in new born babies and significant morbidity and mortality in transplant patients. In this project we are testing a novel nanoparticle-based vaccine formulation which stimulates the immune system with single injection and the immunity induced is sustained for long-term.
Investigating The Function Of Natural Killer Cells During Immunological Responses Following Human Lung Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$71,766.00
Summary
The immune system is critical in controlling common viral infections in healthy individuals. When transplanting foreign solid organs into patients with end-stage lung disease the immune systemÍs activity is decreased via the immunosuppressive drugs to enable graft acceptance. In some patients the immune response can detect similarities between previously encountered viruses and the foreign organ, leading to life-threatening health problems through either rejection episodes and/or graft loss.