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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
CD44 gene vaccination for insulin-dependent diabetes mellitus in non-obese diabetic mice
Lola Weiss1, Ana Maria Botero-Anug, Carla Hand
1Department of Bone Marrow Transplantation and Cancer Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Background:
Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.
Objectives:
To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM in a transfer model of NOD mice.
Methods:
Our vaccination technique involved the insertion of CD44s or CD44v cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN were implanted 20 days before and 3 days after cell transfer.
Results:
In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.
Conclusions:
These findings may open new opportunities for IDDM therapy in the future.
Insights
CD44 gene vaccination, using a virtual lymph node method, protected NOD mice from developing insulin-dependent diabetes mellitus (IDDM). This CD44 immune reactivity strategy shows promise for future IDDM therapies.
Area of Science:
- Immunology
- Molecular Biology
- Endocrinology
Background:
- Standard CD44 and its variants are linked to tumor metastasis and immune cell migration in conditions like diabetes.
- CD44 plays a role in the inflammatory processes involved in experimental insulin-dependent diabetes mellitus (IDDM).
Purpose of the Study:
- To determine if inducing anti-CD44 immune responses via cDNA vaccination can reduce IDDM in a NOD mouse model.
- Investigate the potential of CD44-targeted gene vaccination as a therapeutic strategy for IDDM.
Main Methods:
- cDNA vaccination using CD44s or CD44v inserted into a virtual lymph node (VLN) implant.
- VLNs were implanted in NOD mice before and after transfer of diabetogenic spleen cells.
Main Results:
- Vaccination with CD44s or CD44v cDNA-VLN conferred significant resistance to IDDM in recipient mice.
- The protective effect appears mediated by anti-CD44 antibodies, not cellular immunity.
- Histopathology showed protected pancreatic islets in vaccinated mice compared to destroyed islets in controls.
Conclusions:
- CD44 gene vaccination effectively prevented IDDM development in a mouse model.
- These findings suggest a novel therapeutic avenue for treating insulin-dependent diabetes mellitus.
