T cells are a central component of the immune system. Two main subsets -alpha beta and gamma delta (gd)- can be described, according to the composition of the cell membrane receptors they use to detect antigen. gd T cells usually constitute a small proportion of blood lymphocytes (1-5%), but are enriched at barrier sites, such as the skin and the intestine, where they reside in close contact with epithelial cells. Their location at key sites of infection and cellular transformation, together with their ability to detect tissue perturbations, are ideal properties for a natural immunosurveillance compartment. This has been highlighted recently by their identification as the single most significant human immune population correlating with a favourable cancer prognosis. Nonetheless, despite much effort on elucidating the mechanisms of T cell activation and the cells’ involvement in host protection, much of the biology of gd T cells remains obscure. To address this, it is important to consider how these specialised lymphocytes interact with specific host tissues.
This project sought to elucidate the biology of uterine gd T cells, one of the least understood populations of gd T cells. For example, their spatial and temporal location relative to the uterine epithelium and stroma are ill-defined. Moreover, there is little understanding of T cells more generally in the reproductive tract, a site highly vulnerable to infection and malignant transformation, and a common focus of medical intervention.
In this context the overarching goals for this project were:
1- To characterize and define the function of uterine gd T cells. In this aim, we determined the precise tissue localisation, dynamics and functional properties of uterine gd T cells.
2- To identify the endogenous and environmental mechanisms regulating uterine gd T cells. In this aim, we sought to identify and characterise candidate molecules that regulate the development and/or maintenance of uterine gd T cells, asking whether they act via generalisable mechanisms in common with skin and gut gd T cells, or whether they are unique. Additionally, we studied whether the microbiome regulates the development and/or function of uterine gd T cells, as has been claimed to be the case for some other gd T cell compartments.
Our data have generated the most comprehensive analysis to date of gd T cells in the murine uterus, highlighting their localisation within the uterine stroma and their population kinetics. We have also shown that the cells express a set of characteristic molecules, among which is the proinflammatory mediator IL-17A, which is associated with protection against fungal infections. Indeed, despite being dispensable for normal pregnancy, gd T cells played a critical role in protection of the female reproductive tract against Candida albicans infection.
