Are T-cells the culprit?
In immune-mediated diseases the patient’s immune system is responsible for causing severe damage at targeted sites of the body, be it the brain, joints, gastrointestinal tract or skin. In these conditions, it is expected that the immune cells in the blood, which usually act to clear the body of infections, inappropriately attack the healthy cells of patients leading to the manifestations of the disease.
Blood samples from individuals with the chronic spinal arthritis ankylosing spondylitis (AS) are being used to study the involvement of key genes thought to drive inappropriate immune responses in this disease. Specifically, this project focusses on a group of immune cells called T-cells, and the surface receptors used by these cells to engage with the body’s cells when monitoring for infection. Immunosequencing is a new technique that has been used across the world to look for patterns in T-cell receptor usage by sequencing the genes that encode them. Globally this powerful approach to large-scale sampling of the immune cell population has revelled T-cells associated with immune-diseases, response to infection and anti-tumour immunity. We hope to find T-cell populations that may be targeting inflammatory responses to the sites implicated in AS, the spine, pelvis and gastrointestinal tract.
An visual example of the different gene segments (referred to as ‘variable’ V-genes) used by CD4+ T-cell populations in different individuals (proportions in the total sequenced CD4+ repertoire).