MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
Identifying T Cell Correlates Of Protective Immunity To Malaria In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$396,026.00
Summary
Malaria claims nearly one million lives each year, mostly children. Although those living in endemic regions can acquire natural immunity, it develops slowly and isn`t completely protective. This project studies the impact of different levels of malaria exposure and age on the development of a protective immune response in children. By understanding the effect of high malaria exposure in the development of immunity it is hoped that new avenues for drug development may be identified.
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.
The Cell Death Mechanisms That Control Regulatory T Cell Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$583,782.00
Summary
A central question in immunology is how to prevent destructive immune responses (e.g. autoimmune disease) and initiate productive immune responses (e.g. against cancer). A major breakthrough in this area was the discovery of special immune cells, called a Regulatory T Cells. We propose to discover the genes that determine whether these cells live and die. We will use this information to control appropriate numbers and function of Regulatory T Cells to modify the immune system.
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
Immune Imprinting By Nanoparticles And Vaccines: New Principles And Translation Into The Clinic
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Vaccines require adjuvants to be effective. Despite decades of research there is only one adjuvant approved for broad use in humans. Based on our prior findings I will engage new principles in nanotechnology, and deepen understanding of immune imprinting in various organs of the body including the lung, to develop 2nd generation broadly useful nanoadjuvants able to effectively treat cancer and malaria.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?