Immunotherapy in Autoimmune Type 1 Diabetes

Abstract

■ AbstractType 1 diabetes (T1D) is a chronic autoimmune disease affecting millions of people worldwide. The disease is characterized by the loss of self-tolerance to the insulin-producing β-cells in the pancreas, the destruction of β-cells, and finally the development of chronic hyperglycemia at diagnosis of T1D. Its incidence and prevalence are rising dramatically, highlighting the need for immunotherapeutic strategies able to prevent or treat the disease in a safe and specific manner. Immunotherapeutic strategies are being developed, and aim to restore immunological self-tolerance, thereby limiting unwanted immunity and β-cell destruction. Foxp3 + regulatory T (Treg) cells exert essential functions to maintain and restore immunological self-tolerance. The identification of the transcription factor Foxp3 as the specification factor for the Treg cell lineage facilitated our understanding in the biology of Treg generation and function. This review highlights the current understanding of immunotherapeutic approaches as preventative and curative measures for autoimmune T1D. It includes an overview on early immunointervention studies, which made use of general immunosuppressive agents such as cyclosporin A, followed by a discussion on newly emerging clinical trials. Besides non-antigenspecific therapies, particular attention is given to antigenspecific generation of Foxp3 + Treg cells and their potential use to limit autoimmunity such as T1D.

Targeted Antigen Delivery to DEC-205+Dendritic Cells for Tolerogenic Vaccination

“…Additional evidence that DEC-205 + DC targeting may represent a suitable approach to prevent destructive autoimmunity was provided by studies in mouse models of experimental autoimmune en-cephalomyelitis (EAE), which recapitulate many aspects of human multiple sclerosis [83]. In C57BL/6 mice, high-dose DEC-205+ DC targeting (15 µg) of a myelin oligodendrocyte glycoprotein (MOG)-derived encephalogenic peptide prevented the induction of EAE by the same peptide in complete Freund's adjuvant, through Ag-specific deletion and anergy induction in residual MOGreactive T cells [58].…”

The beneficial effect of growth hormone treatment on islet mass in streptozotocin‐treated mice

“…Type 1 diabetes (T1D) is an autoimmune disease. It is characterized by a loss of pancreatic β ‐cell mass, which results in dramatic reductions in insulin secretion and circulating insulin levels . Recently, there has been a significant increase in the incidence of T1D, and its early onset at 5 years of age will soon be doubled .…”

“…It is characterized by a loss of pancreatic β ‐cell mass, which results in dramatic reductions in insulin secretion and circulating insulin levels . Recently, there has been a significant increase in the incidence of T1D, and its early onset at 5 years of age will soon be doubled . Researchers, for many years, have been searching for therapies that halt the progression of the disease and improve β ‐cell mass and quality of life of the patients.…”

“…Researchers, for many years, have been searching for therapies that halt the progression of the disease and improve β ‐cell mass and quality of life of the patients. Several approaches were tested including immunosuppressive therapies, which had many side effects , islets and pancreas transplantations and other therapies such as glucagon like peptide‐1 (GLP‐1) , with the only real success coming from pancreatic transplantation that accompanies renal transplantation.…”

Alternative Medicine in Diabetes - Role of Angiogenesis, Oxidative Stress, and Chronic Inflammation

“…The array of treatment options is continuously expanding, with new options for type 1 and 2 diabetes patients suffering from different symptoms [17,18]. New drugs in development based on natural substances could help in the management of both types of diabetes [19].…”