The body keeps a careful tally of T cells—immune cells that fight infection—and when that count goes wrong, the result can be autoimmune disease, leukaemia, or immune collapse in AIDS or cancer therapy. Two signals govern T cell numbers: the T cell antigen receptor (TCR), which helps cells recognise pathogens, and a hormone called interleukin-7 (IL7). Researchers know both are involved, but not exactly how they work together to control T cell survival and replication. This project uses specially engineered mice in which each signal can be switched on or off independently, allowing the team to watch what happens to T cells when one or both signals are missing. This is fundamental science. The immediate goal is to understand a basic biological balancing act—how the immune system keeps its cell numbers stable. But the clinical stakes are high. When the balance fails, too many T cells can drive leukaemia or autoimmunity; too few leaves patients vulnerable to infection. A clearer picture of how TCR and IL7 signals cooperate could eventually guide treatments that restore T cell numbers after bone marrow transplants, protect them during chemotherapy, or rein them in when they attack the body’s own tissues.
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The Immune System plays a vital role in protecting individuals from parasitic infections by bacteria, viruses and other disease causing pathogens .T lymphocytes are immune cells that play a key role in regulating immune responses and having them in sufficient numbers is vital if they are to function properly. The number of T cells found in the immune system is carefully regulated by processes that control the production, survival and replication of T cells. Understanding how these processes work is important because when they go wrong, making too many T cells or the wrong type can cause autoimmune diseases such as diabetes or cause development of leukaemia or other cancers. Understanding how our bodies control T cell numbers are controlled also has clinical implications for developing treatments for conditions where T cell numbers are lost, for example in AIDS patients, for people undergoing cancer therapies which have the unwanted side affect of killing T cells or indeed for aiding reconstitution of bone transplant patients.All T cells express a surface protein, the T cell antigen receptor (TCR), that allows T cells to recognise and remember foreign pathogens. However, signals from this same receptor are also involved in controlling T cell survival and replication processes that are involved in controlling the size of the immune system. In addition, a soluble immune hormone, interleukin 7 (IL7) is also involved in regulating these same process and works together with TCR signals. The aim of our work is to gain a deeper understanding of how these two factors control the survival and replication of T cells. In order to do this, we have developed mouse models in which we can specifically control whether T cells receive signals from either the TCR or from IL7. By observing the behaviour and function of T cells in different situations, we can start to better understand how and when these factors are involved in controlling T cell numbers and how they can go wrong to cause disease.
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