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Updated: Jun 10, 2026
Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Dendritic cells transduced to express interleukin 4 reduce diabetes onset in both normoglycemic and prediabetic
Melanie A Ruffner1, Paul D Robbins
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Background:
We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown.
Methodology/Principal Findings:
DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150 mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 10(6) DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals.
Conclusions:
Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D.
Insights
Genetically modified dendritic cells (DC) expressing interleukin-4 (IL-4) can prevent and reverse type 1 diabetes (T1D) in NOD mice. This therapy shows promise for treating autoimmune diabetes by reducing disease progression and inflammation.
Area of Science:
- Immunology
- Endocrinology
- Cell Therapy
Background:
- Previous studies show IL-4 expressing dendritic cells (DC) reduce pathology in autoimmune models.
- IL-4 DC treatment in NOD mice delays hyperglycemia onset, but mechanisms and reversal potential are unknown.
Purpose of the Study:
- To investigate the therapeutic potential of IL-4 expressing DC in preventing and reversing autoimmune diabetes in NOD mice.
- To elucidate the mechanisms underlying the protective effects of IL-4 DC.
Main Methods:
- Bone marrow-derived DC from NOD mice were engineered to express IL-4 (DC/sIL-4) or control vectors.
- DC/sIL-4 or control DC were adoptively transferred into normoglycemic or prediabetic NOD mice.
- Disease progression, islet infiltration, FoxP3 expression, and cytokine profiles were analyzed.
Main Results:
- DC/sIL-4 treatment significantly reduced diabetes incidence in normoglycemic and prediabetic NOD mice.
- DC/sIL-4 administration decreased insulitis and increased FoxP3+ cells in pancreatic lymph nodes.
- Treatment modulated Th2:Th1 cytokine balance, favoring a regulatory profile.
Conclusions:
- Adoptive transfer of IL-4-expressing DC is an effective strategy for treating type 1 diabetes in NOD mice.
- This therapy demonstrates efficacy in both preventing disease onset and reversing established prediabetic conditions.
