ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Genetic-induced variations in the GAD65 T-cell repertoire governs efficacy of anti-CD3/GAD65 combination therapy in new-onset type 1 diabetes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group.Clinical and experimental immunology · 2010Guideline
- Review
- Vaccine for Diabetes-Where Do We Stand?International journal of molecular sciences · 2022Review
- Leverage biomaterials to modulate immunity for type 1 diabetes.Frontiers in immunology · 2022Review
- The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine.Frontiers in immunology · 2021Article
- Twins and endocrinology.Indian journal of endocrinology and metabolism · 2014Review
- Combination therapy with an anti-IL-1β antibody and GAD65 DNA vaccine can reverse recent-onset diabetes in the RIP-GP mouse model.Diabetes · 2014Article
- Progress in immune-based therapies for type 1 diabetes.Clinical and experimental immunology · 2013Review
- Heat shock protein bystander antigens for peptide immunotherapy in autoimmune disease.Clinical and experimental immunology · 2013Review
- Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune diabetes in combination with anti-CD3.Diabetes · 2012Article
- Antigen-specific therapeutic approaches in Type 1 diabetes.Cold Spring Harbor perspectives in medicine · 2012Review
- Antigen-specific prevention of type 1 diabetes in NOD mice is ameliorated by OX40 agonist treatment.Journal of autoimmunity · 2011Article
- Noninsulin pharmacological management of type 1 diabetes mellitus.Indian journal of endocrinology and metabolism · 2011Article
- Humanizing animal models: a key to autoimmune diabetes treatment.Science translational medicine · 2011Article
- Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes.Human vaccines · 2011Review
- Virtual optimization of nasal insulin therapy predicts immunization frequency to be crucial for diabetes protection.Diabetes · 2010Article
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To enhance efficacy of forthcoming type 1 diabetes (T1D) clinical trials, combination therapies (CTs) are envisaged. In this study, we showed that efficacy of a CT, using anti-CD3 antibody and glutamic acid decarboxylase of 65 kd (GAD65)-expressing plasmid, to reverse new-onset T1D was dependent upon the genetic background. Synergism between both treatments was only observed in the RIP-LCMV-GP but not in the nonobese diabetic (NOD) or RIP-LCMV-NOD models. Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma). In addition, we found that frequency and epitope specificity of GAD65-reactive CD4(+) T cells during antigen priming at diabetes onset and Tregs detected after CT correlated. Consequently, NOD mice harbored significantly lower levels of GAD65-reactive CD4(+) T cells than RIP-LCMV-GP before and after treatment. Our results demonstrate that antigen-specific T cells available at treatment may differ between various major histocompatibility complex (MHC) and genetic backgrounds. These cells play a major role in shaping T-cell responses following antigen-specific immune intervention and determine whether a beneficial Tregs response is generated. Our findings hold important implications to understand and predict the success of antigen-based clinical trials, where responsiveness to immunotherapy might vary from patient to patient.
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