King's College London

T-bet (Tbx21) was first discovered to have a role in the adaptive immune system almost 20 years ago. It was found to be a key regulator in the function of CD4⁺ T helper 1 (TH1) cells. T-bet has been shown to be expressed and have a function in the other subsets of T helper cells. Understanding the role of T-bet and the role it plays in T cell differentiation and plasticity has become vital, as well as, the function of T-bet in other immune cells. 
Within the lab, a new mouse line has been developed that is able to fluorescently trace the lineage of T-bet expressed cells. Experiments have involved phenotyping this mouse line and determining the base-line level of T-bet expressing cells within each cell compartment. Further experiments will investigate the expression level of fate mapped T-bet cells, mainly the CD4⁺ T cells, in disease models in this mouse line. 
Further analysis of these T-bet traced cells have been performed to see whether these cells are more plastic and able to illicit a switch to a TH1 response and if there is a developmental aspect to expressing T-bet in development of CD4⁺ T cells. This thesis looks into these cells in more depth. I also have had the use of another mouse line which is able to delete T-bet in cells using tamoxifen treatment. This mouse line has given me the chance to delete T-bet from CD4⁺ T cells after they have developed and see if there is any change in plasticity and, also compare them with the deletion of T-bet in innate lymphoid cells. 
Finally, I have also used another mouse line which deletes T-bet in specifically regulatory T cells. This mouse line was used in a heart transplant model to see whether the deletion of T-bet would have any effect in the ability of Tregs to aid in tolerance of the heart transplant and prevent rejection of the graft. 
This thesis aims to learn more about the role of T-bet within the immune response and especially in the CD4⁺ T cell compartment, as despite the on-going research there is still a big unknown area of how the master regulators of CD4⁺ T cells regulate the plasticity and differentiation of these cells. Using these mouse models, I have discovered more about the insight into this and provide suitable and hopefully more understanding towards this subject.