Immune regulation in type 1 diabetes : towards a tissue specific cell therapy

Abstract

Type 1 diabetes is a T-cell mediated autoimmune disease in which the insulin producing cells in the islets of Langerhans are destroyed. No cure exists yet, but multiple types of immune suppressive regimens are explored. In this thesis I studied the opportunities to dampen autoimmunity in type 1 diabetes, with the focus on the possibility of using tolerogenic dendritic cells loaded with islet antigens as cell therapy in patients with type 1 diabetes. Tolerogenic DCs appear suitable candidates to modulate T-cell response at different levels and are able to induce antigen specific regulatory T-cells, utilizing various mechanisms to suppress pro-inflammatory responses. Hence, the chance for successful control of autoimmunity in patients treated with tolerogenic DC therapy may be increased compared to monotherapy. Tolerogenic DCs as cell therapy have the potential to modulate the immune system. Although replacement or enhancement of insulin producing beta-cells is warranted, focusing on diminishing the causal pathology, the immune attack on the islets of Langerhans, could be a preferential option, as it is still difficult to challenge existing autoimmunity with the current arsenal of immunosuppressive drugs. This tissue-specific intervention cell therapy might offer new opportunities for the treatment of type 1 diabetes.