AIMS/HYPOTHESIS: The long-term effects of successful immune therapies for 
treatment of type 1 diabetes have not been well studied. The 
Autoimmunity-Blocking Antibody for Tolerance (AbATE) trial evaluated teplizumab, 
an Fc receptor non-binding humanised anti-CD3 monoclonal antibody in individuals 
with new-onset type 1 diabetes, and ended in 2011. Clinical drug-treated 
responders showed an increased frequency of 'partially exhausted' CD8+ T cells. 
We studied the clinical, immunological and metabolic status of participants 
after an average follow-up of 7 years.
METHODS: Participants with detectable C-peptide at year 2 of AbATE returned for 
follow-up. C-peptide responses were assessed by 4 h mixed-meal tolerance test. 
Autoantibodies and HbA1c levels were measured and average daily insulin use was 
obtained from patient logs. Peripheral blood mononuclear cells were analysed by 
flow cytometry and cytokine release.
RESULTS: Fifty-six per cent of the original participants returned. Three of the 
original control group who did not return had lost all detectable C-peptide by 
the end of the 2 year trial. The C-peptide responses to a mixed-meal tolerance 
test were similar overall in the drug vs control group of participants but were 
significantly improved, with less loss of C-peptide, in drug-treated responders 
identified at 1 year. However, the improvements in C-peptide response were not 
associated with lower HbA1c levels or insulin use. Drug-treated responders 
showed a significantly increased frequency of programmed cell death protein 
1-positive central memory and anergic CD8+ T cells at follow-up.
CONCLUSIONS/INTERPRETATION: These findings suggest there is reduced decline in 
C-peptide and persistent immunological responses up to 7 years after diagnosis 
of diabetes in individuals who respond to teplizumab.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02067923; the protocol is available at 
www.immunetolerance.org (ITN027AI).