Determining the regulation of immune checkpoint co-receptors in an ageing immune system
Principal Investigator: Dr Shoba Amarnath
Our immune system consists of the adaptive immune system and the innate immune system. Specialised cells called T cells make up the adaptive immune system and are vital for protecting our body against pathogens. As we age, our T cells lose their ability to function properly and the underlying reason for this dysfunction remains unknown.
T cells usually need several signals to become activated. One of the signals is controlled by surface receptors known as co-receptors. Co-receptors can either promote T cell activation or inhibit T cell activation, but which co-receptors are highly expressed in an aged T cells, is not clear.
Activation of T cells can also result in bystander immune system activation through the innate immune system. Again, we are not sure what modifications occur within the innate immune cell compartment within the aged immune system.
Studying these two parts of the immune system will enable us to not only understand the ageing immune system in a comprehensive manner but it will also help us to design better vaccination strategies for older adults.
In addition, this will inform clinical trials in diseases like cancer, whereby immunotherapies do not work very well in older patients and we do not know the reason behind this dysfunction.
In this study, using flow cytometry and mesoscale, we will generate pilot data that will:
- Determine the expression pattern and absolute number of co-receptors in ageing T cells
- Determine the heterogeneity of innate immune cells in ageing T cells
On generating these data, we will perform in depth deep sequencing to understand if acquired somatic mutations are associated with dysfunctional T cells and innate immune cells in an ageing population.
This study will be the springboard for developing this field in Newcastle which is in its infancy and requires immediate attention given the ageing UK and worldwide population.