Leiden University Scholarly Publications

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Megen, K.M. van (2021)

From immune suppression to immune modulation in type 1 diabetes patients

Doctoral Thesis
Type 1 Diabetes (T1D) is an auto-immune disease in which beta cells in the pancreas are killed by auto-reactive T-cells. Auto-reactive T-cells are activated by dendritic cells that present antigens. Immunotherapy could reverse T1D, however. A case report of a T1D patient showed that after intravenous immunoglobulin treatment her insulin needs dropped completely. Similarly, the majority of T1D patients were insulin independent after autologous hematopoietic stem cell transplantation. As these therapies only showed incidental success or are a drastic reset of the immune system, respectively, other milder therapies were studied as well. Autologous tolerogenic dendritic cell therapy, for instance, is a reproducible, stable therapy and does not differ between T1D patients and healthy subjects. In addition, the author described that when mesenchymal stromal cells were activated, they were able to suppress an antigen-specific immune response, thereby potentiating them as an antigen...Show moreType 1 Diabetes (T1D) is an auto-immune disease in which beta cells in the pancreas are killed by auto-reactive T-cells. Auto-reactive T-cells are activated by dendritic cells that present antigens. Immunotherapy could reverse T1D, however. A case report of a T1D patient showed that after intravenous immunoglobulin treatment her insulin needs dropped completely. Similarly, the majority of T1D patients were insulin independent after autologous hematopoietic stem cell transplantation. As these therapies only showed incidental success or are a drastic reset of the immune system, respectively, other milder therapies were studied as well. Autologous tolerogenic dendritic cell therapy, for instance, is a reproducible, stable therapy and does not differ between T1D patients and healthy subjects. In addition, the author described that when mesenchymal stromal cells were activated, they were able to suppress an antigen-specific immune response, thereby potentiating them as an antigen-specific therapy besides their natural immunosuppressive nature. Activated mesenchymal stromal cells could also improve the islet of Langerhans’ microenvironment, as they secreted immunosuppressive and angiogenic factors. To conclude, the future of T1D therapies lies in finding a balance between suppressing the immune system and antigen-specific therapies combined with therapies that increase the vitality of beta cells.
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Type 1 Diabetes
Immune Modulation
Cellular Therapy
Immunotherapy
Dendritic cells
Tolerogenic dendritic cells
Mesenchymal Stromal Cells
Autologous Hematopoietic Stem Cell Transplantation
Autoimmune Disease
Vitamin D3
All authors
Megen, K.M. van
Supervisor
Roep, B.O.; Zwaginga, J.J.
Co-supervisor
Nikolic, T.
Committee
Koning, E.J.P. de; Mathieu, C.; Aanstoot, H.J.; Vries, J.de
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2021-10-05
ISBN (print)
9789090351438

Funding

Sponsorship
Chipsoft en Stichting DON