Control of CD4+ T cell responses by human gamma/delta T cells

γδ T-cells are ’unconventional’ lymphocytes that regulate immune responses to infection and promote mucosal protection.

You will use gene expression profiling and functional studies using cells from human blood and intestine and in vivo models to define how microbe-responsive γδ T-cells control CD4+ T-cells in health and inflammation.

So-called ’unconventional’ lymphocytes sense pathogens, regulate recruitment and function of other immune cells, and help protect the skin and intestine. This project will study how microbe-responsive γδ T-cells in human blood and gut control ’conventional’ CD4+ T-cell responses in health and inflammation. Polarisation of CD4+ T helper cells is crucial for host defence against pathogens and tumours, but also for wound healing and resolution of inflammation. Better understanding of this process will therefore inform the development of novel vaccines, treatments and diagnostics for a range of human pathologies.

Our recent data demonstrate a striking plasticity of γδ T-cells to modulate immunity at epithelial sites and during infection. A previous PhD student already identified γδ T-cell signals that drive expression of the tissue-protective factors IL-22 and calprotectin in the intestine. Unpublished work shows that γδ T-cells can also induce regulatory and anti-inflammatory CD4+ T-cell responses.

The objective of this project is to define the molecular mechanisms underlying CD4+ T-cell polarisation by γδ T-cells and identify ways to manipulate them for future interventions. You will work across disciplinary boundaries, by combining functional studies using murine and human cells, bioinformatics approaches, analyses of human intestinal biopsies, and in vivo models of inflammation.

For further details of this project, please see our website: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/project/control-of-cd4-t-cell-responses-by-human-gammadelta-t-cells