T cell immunity to islets of Langerhans : relevance for immunotherapy and transplantation to cure type 1 diabetes

Huurman, V.A.L. (2009)

Doctoral Thesis

Type 1 diabetes is a common, multifactorial disease in which T cell autoimmunity plays an important role. Important research advances in recent years have fuelled the expectation that a definitive cure for the disease can be achieved for a large number of patients. In the first part of this thesis, the considerable clinical and immunological potential for intervention in the diabetogenic autoimmune process is described of the T cell costimulatory molecule CTLA4 and the autologous heat shock protein peptide DiaPep277. The second part focuses on islet and pancreas transplantation as a cure for type 1 diabetes. Next to the influence of allograft rejection and the effects of immunosuppressive therapy, associations are described between the presence and recurrence of diabetes-specific autoimmunity and clinical outcome of transplantation. Furthermore, possible factors are identified that may be modulated for improvement of outcome, and predictive biomarkers are suggested that may guide future treatment. In conclusion, this thesis recognizes T cell autoimmunity as an important entity in type 1 diabetes therapy, distinct from other types of immune reactivity. Tailored therapy for individual patients guided by close immune monitoring is being developed but needs to be improved further to establish a definitive cure for type 1 diabetes.

• Type 1 diabetes
• Immunotherapy
• Islet transplantation
• Pancreas transplantation
• Autoimmunity
• Alloimmunity

• All authors: Huurman, V.A.L.
• Supervisor: Terpstra, O.T.
• Co-supervisor: Roep, B.O.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-03-04
• Sponsorship: Diabetes Fonds Nederland, J.E. Jurriaanse stichting, Eli Lilly Nederland BV, U-Cytech BV, Novo Nordisk BV, Novartis Pharma BV and Roche Nederland BV.