An investigation of the role of regulatory T cells in childhood T1DM
Research type
Research Study
Full title
An investigation into the role of regulatory T cells in children with Type 1 Diabetes Mellitus
IRAS ID
185037
Contact name
Paul Johnson
Contact email
Sponsor organisation
Oxford University Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 1 days
Research summary
Research Summary
Type 1 diabetes mellitus (T1DM) is the most common chronic disease of childhood. T1DM is caused by destruction of the pancreatic beta cells by an abnormal immune response. This leads to loss of glucose metabolism and significant short and long term complications.Treatment with regular insulin administration can reduce the long term complications of T1DM but is not curative.
Regulatory T Cells (Tregs) are present in circulating blood in small numbers and have the ability to suppress the body’s immune response. Our research group has previously been involved in the analysis, isolation and expansion of Tregs for human administration in renal transplantation.
Some studies have demonstrated a reduced frequency of Tregs in patients suffering T1DM but this finding has not been confirmed. Many previous studies have been performed on adult patients. A difference in Treg function in T1DM has also been suggested to play a role in pathology.
Further research into the role of Tregs in T1DM is important as they may help characterise the cause of T1DM and highlight potential therapeutic interventions. This research may also help develop novel cellular therapies for immuno-suppression in islet transplantation.
In this study we aim to collect blood samples from 19 healthy children and 19 with T1DM who are already having routine blood tests or intravenous access for elective surgery. We will accurately analyse the frequency of Tregs in all. In a small number of participants (5 in each group), all undergoing surgery, we will take a relatively larger sample to isolate and expand Tregs to measure function. These novel results will allow more thorough assessment of Treg function and will clearly define the differences in frequency and function of Tregs in children with T1DM highlighting future possible clinical interventions.Summary of Results
Type 1 Diabetes Mellitus (T1DM) is the most common chronic disease of childhood. Regulatory T-Cells (Treg) can been expanded in the lab to be used as a personalised treatment to dampen the patients immune response.This study aimed to characterise whether there is a difference in Treg in children recently diagnosed with T1DM and whether expansion of paediatric Treg is feasible.
To do this blood samples were collected from children (3-16yr) undergoing annual review (T1DM) or day case surgical procedure (Healthy Controls). All samples underwent immune cell analysis for Treg and other immune populations (Flow Cytometry in all, and n=10 using a 38 marker panel mass cytometry/ CyTOF technique) . In a smaller group a relatively larger (<30ml) sample was taken to study feasibility of Treg isolation and expansion.
42 participants were recruited (T1DM = 22, Control = 20).
4 participants (3 control, 1 T1DM) had good expansion of Treg (median 71x range 53-220x). No significant difference in the frequency of Treg in T1DM was seen.To conclude children recently diagnosed with T1DM appear to shows similar Treg markers to healthy controls. Both with traditional flow cytometry and higher dimension CyTOF.
Expansion of paediatric Treg is feasible. Together these results reveal new features of Treg in T1DM and have important implications for the use of expanded Treg therapies in paediatric T1DM
REC name
Wales REC 7
REC reference
16/WA/0059
Date of REC Opinion
10 Feb 2016
REC opinion
Favourable Opinion