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Critical roles of CD30/CD30L interactions in murine autoimmune diabetes
S Chakrabarty1, M Nagata, H Yasuda
1Division of Internal and Geriatric Medicine, Department of Development and Ageing, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
CD30/CD30L is a member of tumour necrosis factor (TNF) receptor/TNF superfamily and has been implicated in immune-regulation. A genetic study has also suggested a possible implication of CD30 in spontaneous autoimmune diabetes in NOD mice. In this study, we investigated the involvement of CD30/CD30L in the development of diabetes in NOD mice. Flow cytometric analysis showed that CD30 and CD30L were highly expressed on CD4+ or CD8+ T cells in the spleen and pancreatic lymph node of younger NOD mice. In addition, islet-specific CD4+ or CD8+ T cell lines expressed CD30 and CD30L. Administration of a neutralizing anti-CD30L monoclonal antibody (mAb) from 2 to 10 week of age completely suppressed the development of spontaneous diabetes in NOD mice. In addition, the treatment with anti-CD30L mAb also inhibited the development of diabetes induced by adoptive transfer of spleen cells from diabetic NOD mice or islet-specific CD4+ or CD8+ T cell lines into NOD-SCID mice. Furthermore, anti-CD30L mAb inhibited T cell proliferation in response to islet antigens. These results suggested that CD30/CD30L interaction plays important roles in both induction and effector phases of autoimmune diabetes in NOD mice.
Insights
The CD30/CD30L pathway is crucial in the development of autoimmune diabetes in NOD mice. Blocking CD30L with an antibody prevented diabetes, suggesting a therapeutic target for immune-regulation.
Area of Science:
- Immunology
- Endocrinology
- Autoimmunity
Background:
- CD30/CD30L, part of the TNF superfamily, is involved in immune regulation.
- Previous studies suggested CD30's role in spontaneous autoimmune diabetes in NOD mice.
Purpose of the Study:
- To investigate the role of CD30/CD30L in the development of autoimmune diabetes in NOD mice.
Main Methods:
- Flow cytometry to analyze CD30/CD30L expression on T cells.
- Administration of anti-CD30L monoclonal antibody (mAb) in NOD mice.
- Adoptive transfer experiments and T cell proliferation assays.
Main Results:
- CD30 and CD30L were highly expressed on T cells in young NOD mice.
- Anti-CD30L mAb treatment completely suppressed spontaneous diabetes development.
- Treatment inhibited diabetes induced by adoptive transfer and T cell proliferation.
Conclusions:
- CD30/CD30L interaction is critical for both the induction and effector phases of autoimmune diabetes in NOD mice.
- Targeting CD30L may be a potential therapeutic strategy for autoimmune diabetes.