ArticleDiabetologia2012
Low doses of anti-CD3, ciclosporin A and the vitamin D analogue, TX527, synergise to delay recurrence of autoimmune diabetes in an islet-transplanted NOD mouse model of diabetes.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Vitamin D and Beta Cells in Type 1 Diabetes: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Combined Use of Vitamin D and DPP-4 Inhibitors as a Potential Adjuvant Treatment Strategy to Enhance the Efficacy of Novel Beta-Cell Replacement Therapies for Type 1 Diabetes.Medical sciences (Basel, Switzerland) · 2025Review
- Type 1 Diabetes Autoimmunity: To What Extent Vitamin D is Beneficial.Biochemistry research international · 2025Review
- Vitamin D's Effect on Immune Function.Nutrients · 2020Review
- miR-409-3p is reduced in plasma and islet immune infiltrates of NOD diabetic mice and is differentially expressed in people with type 1 diabetes.Diabetologia · 2020Article
- Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule.Frontiers in endocrinology · 2020Review
- Intestinal Delivery of Proinsulin and IL-10 viaFrontiers in immunology · 2020Article
- Article
- Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity.Nature communications · 2017Article
- Article
- Human multipotent adult progenitor cells enhance islet function and revascularisation when co-transplanted as a composite pellet in a mouse model of diabetes.Diabetologia · 2017Article
- Vitamin D improves diabetic nephropathy in rats by inhibiting renin and relieving oxidative stress.Journal of endocrinological investigation · 2016Article
- Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.PloS one · 2014Article
- Combining MK626, a novel DPP-4 inhibitor, and low-dose monoclonal CD3 antibody for stable remission of new-onset diabetes in mice.PloS one · 2014Article
- Biologic agents in islet transplantation.Current diabetes reports · 2013Review
- Vitamin D, immune tolerance, and prevention of type 1 diabetes.Current diabetes reports · 2012Review
- Animal models of diabetes mellitus for islet transplantation.Experimental diabetes research · 2012Review
- Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisAnti-CD3 monoclonal antibodies remain the most promising immune therapy for reversing recent-onset type 1 diabetes. However, current clinical trials have revealed their major drawback, namely the narrow therapeutic window in which low doses are ineffective and higher doses that preserve functional beta cell mass cause side effects. Strategies that sidestep these limitations while preserving or improving anti-CD3's therapeutic efficiency are essential. We hypothesised that combining a potent vitamin D(3) analogue (TX527), ciclosporin A (CsA) and anti-CD3 would act to lower the dose while maintaining or even boosting therapeutic efficacy to counteract autoimmune destruction of transplanted islets.
methodsThis study involved the use of syngeneic islet transplantation, immunofluorescence microscopy, immune phenotyping by flow cytometry, RT-PCR analysis, and in vitro and in vivo suppression assays.
resultsCombination therapy with TX527, CsA and anti-CD3 was well tolerated on the basis of weight, bone and calcium variables. Remarkably, combining all three agents at sub-therapeutic doses greatly reduced recurrent autoimmune responses to a grafted islet mass (mean ± SEM: 79.5 ± 18.6 days; p < 0.01), by far exceeding the therapeutic efficacy of monotherapy (24.8 ± 7.3 days for anti-CD3) and dual therapy (25.5 ± 12.4 days for anti-CD3+CsA). Combination therapy surpassed anti-CD3 monotherapy in reducing islet infiltration by effector/memory phenotype CD8(+) T cells, as well as by reducing proinflammatory cytokine responses and increasing the frequency of T regulatory cells that were functional in vitro and in vivo, and acted in a cytotoxic T lymphocyte antigen 4-dependent manner. CONCLUSIONS/
interpretationCombining the immunomodulatory actions of anti-CD3 mAb with CsA and the vitamin D(3) analogue, TX527, delivers therapeutic efficacy in an islet-transplanted NOD mouse model of diabetes.
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