Destruction, regeneration and replacement of beta-cells and aspects of immune-intervention in type 1 diabetes

Alkemade, G.M. (2016)

Doctoral Thesis

 

In this thesis, in close collaboration with my research colleagues, I have shown that T-cell recruitment in both spontaneous autoimmune diabetes and islet transplantation requires presence of a cognate antigen, which could be used as an argument in favour of further pursuing antigen-specific therapies. We have shown that recurrent diabetes in an islet transplantation model is driven by memory auto reactive T-cells and this latter finding has contributed to the present testing of immune suppressive drugs that indeed address recurrent autoimmunity, to improve outcome in clinical islet transplantation. We have designed and tested a novel auto-immune diabetes cell line tracing model for future testing of the regenerative capacity of islet-cells. We have shown that immune evasion protects beta-cells from autoimmune T-cell attack in vivo. Currently different immune evasion techniques, such as islet encapsulation are being tested in the clinic. We have shown that recall immunity is preserved in spite of high dose anti-CD3 treatment, adding to the safety of high dose anti-CD3 treatment as an immune modulator agent in the treatment of T1DM.

 

• Destruction
• Regeneration
• Replacement
• Beta-cells
• Immune-intervention
• Type 1 Diabetes
• Islet Transplantation

• All authors: Alkemade, G.M.
• Supervisor: Roep, B.O.; Santamaria, P.
• Committee: Koning, E.J.P. de; Nieuwdorp, M.; Nikolic, T.; Wolffenbuttel, B.H.R.; Zwaginga, J.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine, Leiden University
• Date: 2016-05-19
• ISBN (print): 9789402800609