We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
Molecular Regulation Of Tim3 Signalling In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Chronic inflammatory diseases like multiple sclerosis and cancer can be rectified via interventions of T cell checkpoint pathway. Tim3 is a T cell checkpoint molecule that is gaining extreme interest in these diseases. Here, we aim to identify molecular mechanism(s) to suppress or enhance Tim3 signalling in effector T cell, potentially leading to the development of therapeutic intervention to treat autoimmune disorders and cancers.
Identifying The Ontogeny And Fate Of T Follicular Helper Cells By Two-photon Photoconversion
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vacc ....The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vaccine design.Read moreRead less
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.
Effector And Memory CD8+ T Cell Responses To Engineered Influenza A Escape Mutants
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
T cells are a critical component of the immune system after infection with viruses. In particular, virus-specific CD8+ T cells can clear viral infections by killing virally-infected cells and the release of immunomodulators. These are called effector T cells. After the viral infection is cleared, a small proportion of T cells (around 5 to 10%) survives for many years and constitute a memory pool of virus-specific T cells. Memory T cells provide a rapid and effective protection in case of a repea ....T cells are a critical component of the immune system after infection with viruses. In particular, virus-specific CD8+ T cells can clear viral infections by killing virally-infected cells and the release of immunomodulators. These are called effector T cells. After the viral infection is cleared, a small proportion of T cells (around 5 to 10%) survives for many years and constitute a memory pool of virus-specific T cells. Memory T cells provide a rapid and effective protection in case of a repeated infection with the same virus, and hence result in a less severe disease. However, viruses often mutate their genes to escape such efficient T cell responses. In this study, we will investigate T cell responses after infection with mutated strains of influenza viruses. We will engineer a panel of mutant influenza viruses, which alter the nature and characteristics of T cells. We will analyse how efficient are these T cells and whether they can protect against a normal strain of influenza A. Subsequently, we will characterise quantitative and qualitative aspects of memory T cell pools after infection with mutant influenza viruses. Since a number of viruses such as influenza, HIV and HCV rapidly mutate their genes, our study will not only address the question of T cell responses to mutated influenza viruses, but also will provide an excellent model for investigating protective T cell responses to other viral infections.Read moreRead less
Molecular And Cellular Control Of Human Th9 Cell Differentiation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$550,888.00
Summary
T helper 9 (Th9) cells are a recently defined population of CD4+ T cells that have been implicated in immunological disorders ranging from allergy, asthma, inflammatory bowel disease, and cancer, to host defence against fungal and parasitic infections. As such, Th9 cells are extremely important to human health and disease. This project aims to define the mechanisms involved in the generation, regulation and function of human Th9 cells.
Antigen Dose And TCR Repertoire In CD8+ T Cell Immunodominance Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
The CD8+, or killer , T lymphocytes (white blood cells) are the hit men of immunity, recirculating continually around the body to eliminate other cells that are dangerous because they are cancerous or infected with a virus. A major difficulty is that killer T cells also exert selective pressures that cause viruses and tumours to mutate and thus avoid immune control. This is a particularly serious problem for RNA viruses that readily mutate as they divide. These include the human immunodeficiency ....The CD8+, or killer , T lymphocytes (white blood cells) are the hit men of immunity, recirculating continually around the body to eliminate other cells that are dangerous because they are cancerous or infected with a virus. A major difficulty is that killer T cells also exert selective pressures that cause viruses and tumours to mutate and thus avoid immune control. This is a particularly serious problem for RNA viruses that readily mutate as they divide. These include the human immunodeficiency virus (HIV) that causes AIDS and, while the mutations that are most important with influenza viruses are those that modify viral surface proteins recognized by antibodies, such T cell escape mutants can also be a problem with influenza. The other reason why there is particular interest in promoting CD8+ T cell-mediated immunity to influenza is that the killer T cells are very cross-reactive. We have shown that vaccination approaches that prime mouse CD8+ T cells to resist influenza A viruses circulating currently in humans will also protect against the highly lethal, and dangerous H5N1 bird 'flu. The present flu vaccines only stimulate antibodies, so there is interest in the possibility of a major re-design. The CD8+ T cells recognize tiny elements (peptides) of the virus or tumour bound in the tip of our own transplantation, or class I major histocompatibility complex (MHCI) molecules. These pMHCI complexes are called epitopes. The focus here is on the use of novel genetic engineering strategies to find out how, when the virus mutates to disrupt the major epitopes seen by killer T cells, other minor epitopes can be abnormally emphasized in a way that promotes effective immune control. As we work on this with the relatively simple and safe influenza model we will concurrently develop strategies that may be of value in HIV and tumour immunity. Solving this problem could prove to be a substantial advance in the design of vaccines and immunotherapy approaches.Read moreRead less
The Role Of CD1-restricted T Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
The human immune system requires T cells for survival. Specialised populations of T cells exist that patrol the body and target unwanted lipid molecules expressed by bacteria or by cells that have become abnormal or cancerous. I will identify these T cells in human blood and skin and determine their role in protection against disease. I will explore the types of lipids molecules recognised by these T cells and use this information to help prevent human diseases.