Adrian Hayday : Immuno Surveillance

Goals

The group is focused on understanding how lymphocytes function within epithelial tissues. We have developed the “Lymphoid Stress Surveillance” hypothesis whereby tissue-associated T cells recognise and respond to perturbations to epithelia cells. This is an under-studied component of lymphocyte biology, distinct from conventional T cell responses by its rapidity, and by its capacity to monitor perturbations induced by non-microbial challenges, such as carcinogens or oxidative stress. The implications are that tissue-associated T cells can identify and eradicate transformed cells early in the route to malignancy. Consistent with this, the molecular mechanisms of lymphoid stress-surveillance include the engagement by T cells of specific molecules upregulated on epithelial cell surfaces by stresses such as DNA damage or inappropriate progression into the cell cycle. Such molecules are commonly expressed by tumours, and we have shown that the lack of tissue-associated T cells increases the susceptibility to chemical carcinogens. Moreover, tumours and many types of virus employ immuno-evasive strategies to disarm this pathway of surveillance. Ongoing efforts aim to define the full range of molecules and pathways by which tissue-associated T cells can recognize dysregulated epithelial cells, and the functional consequences thereof. Our most recent studies investigate the linkage between lymphoid stress-surveillance and allergy, and likewise between allergy and tumour immune surveillance.