A5049870213- Immune Cell Function and Interaction
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Diabetes Management and Research
- Congenital heart defects research
- CAR-T cell therapy research
- Pancreatic function and diabetes
St Thomas' Hospital
2017-2020
King's College London
2017-2020
Guy's Hospital
2017
Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic local hypersensitivity. Placebo subjects showed a significant decline stimulated C-peptide...
Defects in T cell receptor (TCR) repertoire are proposed to predispose autoimmunity. Here we show, by analyzing >2 × 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4+ subsets from patients with type 1 diabetes healthy donors, that have shorter complementarity-determining region 3s (CDR3), all subsets, introduced increased deletions/reduced insertions during VDJ rearrangement. High frequency short CDR3s is also observed unproductive sequences,...
We previously reported that costimulation blockade by abatacept limits the decline of β-cell function and frequency circulating CD4+ central memory T cells (TCM) (CD45RO+CD62L+) in new-onset type 1 diabetes. In human subjects receiving placebo, we found a significant association between an increase TCM function. To extend refine these findings, examined changes CD8+ naive cell subsets at greater resolution using polychromatic flow mass cytometry. placebo group, successfully reproduced...