Cutaneous Inflammation, Bone Marrow Dendritic Cells, And Implications For Immune Responses And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
With inflammation of the skin due to excessive sun exposure or chemicals, biological signals are sent to the bone marrow where immune fighting cells are generated. However, the immune system must not overreact. We have measured bone marrow derived immune cells with reduced function following skin inflammation which we propose is part of homeostasis. We need to better understand how these cells are altered and for how long they are altered.
Role Of The Thymus In T Cell Homeostasis During Foetal And Postnatal Life In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool e ....The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. It follows that a mixing of the pool of older mature T cells with new ones just released from the thymus will introduce more variability, and hence greater adaptability into the immune system. We have developed techniques for labeling the thymus in vivo and the entire blood leukocyte pool in vivo using the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled cells and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and mature cells and their progeny together with their tissue homing properties and surface markers for periods of many months. This will enable us to determine the way in which the pool of mature T cells is built up during the formation of the foetal immune system and the way the mature T cell population is established and maintained in postnatal life.Read moreRead less
Changes In The Fate Of Thymic Emigrants During Foetal And Postnatal Development In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$62,744.00
Summary
SIGNIFICANCE The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cell, has considerable implications for the development of the T cell repertoire. Recent thymic emigrants represent a wide diversity of positively selected thymocytes but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a l ....SIGNIFICANCE The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cell, has considerable implications for the development of the T cell repertoire. Recent thymic emigrants represent a wide diversity of positively selected thymocytes but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. A high rate of continuous substitution of mature T cells in the peripheral pool with freshly arriving recent thymic emigrants exhibiting newly arising TCR not previously existing will produce higher adaptive capabilities for the immune system. We have developed techniques for labeling the thymus in vivo by intra-thymic injection with the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled recent thymic emigrants and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and their progeny together with their tissue homing properties and surface markers for periods of many months after they leave the thymus. This will enable us to determine the way in which the pool of mature T cells is built up during the formation of the foetal immune system and the way the mature T cell population is established and maintained in postnatal life.Read moreRead less
Dendritic Cell Function, Migration And Modulation In A Murine Model Of Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$201,870.00
Summary
Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In ....Rheumatoid arthritis (RA) is a debilitating disease that affects the joints and other tissues. While it can often be controlled with drugs, complete remission off treatment is rare. Dendritic cells are the educators of the immune system. By displaying antigen to T cells they communicate the response that the immune system should make to foreign organisms, tumors and to self. Therefore, a communication failure may result in chronic inflammation, tumor growth or autoimmune disease, such as RA. In this proposal, we focus on the role of dendritic cells in a mouse model of RA and explore ways of using dendritic cells to turn off disease, that if successful may translate in humans to induction of remission.Read moreRead less