Researchers at the Snow Centre for Immune Health have uncovered subtle but consistent differences in immune cell behaviour in people with coeliac disease, suggesting risk may arise from how the immune system functions long before symptoms appear.
The new study, published in Immunology & Cell Biology, tracked early immune responses and found that CD4 helper T cells displayed weaker signalling, slower activation and reduced survival, challenging the idea that autoimmunity is simply an overactive immune response.
Led by Dr Vanessa Bryant, Professor Phil Hodgkin and Dr Susanne Heinzel with clinical input from Snow Centre Director Professor Jason Tye Din, the team used a novel approach to measure what they call immune momentum.
Rather than continuously stimulating cells as most laboratory tests do, they briefly activated T cells, then removed all signals to observe how the cells behaved afterwards.
“Our assay is a bit like winding up a toy and letting it go to see how long it runs and what tricks it performs,” Dr Bryant said. “Our method reveals how well T cells read and store their activation signals to maintain their ‘momentum’ once the original stimulus is gone and whether people with autoimmune disease have built-in differences in how their cells function.”
Using the centre’s Cyton2 Cell Timer model, the researchers tracked cell division, survival and production of key signalling molecules. Instead of the expected overactivity, T cells from people with coeliac disease produced less interleukin-2, entered cell division more slowly, and were less likely to survive.
“These differences were subtle but remarkably consistent,” Dr Bryant said.
The pattern held across sexes and regardless of whether individuals were newly diagnosed or managing the condition on a gluten-free diet, indicating the effect is not simply driven by inflammation or diet and may be linked to genetic risk.
The findings could have implications beyond coeliac disease. Many autoimmune conditions share overlapping genetic risk factors and affect around five per cent of the population. “
If autoimmune risk is partly built into how immune cells behave from the start, this could change how we think about early detection,” Dr Bryant said. While the approach remains a research tool rather than a clinical test, it points toward combining genetic information with functional immune measurements to improve risk prediction and personalised monitoring.
Professor Tye Din highlighted the value of the Cyton cell timer for revealing hidden patterns in immune function. “This gives us a new way to understand immune behaviour in greater detail. My hope is that these fundamental insights will eventually translate into clinically useful tools to inform assessments of disease risk.”
The team is now investigating whether similar immune patterns appear in other autoimmune conditions and how early in life these differences emerge. “Our long-term goal is to understand autoimmune risk well enough that we can act earlier, potentially even before disease begins,” Professor Tye Din said.