Inhibition of autoimmune diabetes by TLR2 tolerance.

Treatment of Autoimmune Diabetes by Inhibiting the Initial Event

Recent papers have shown that the initial event in the pathogenesis of autoimmune type 1 diabetes (T1D) comprises sensing of molecular patterns released from apoptotic β-cells by innate immune receptors such as toll-like receptor (TLR). We have reported that apoptotic β-cells undergoing secondary necrosis called 'late apoptotic' β-cells stimulate dendritic cells (DCs) and induce diabetogenic T ...

Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes.

Although it is established that defective clearance and, hence, increased accumulation of apoptotic cells can lead to autoimmunity, the mechanism by which this occurs remains elusive. Here, we observed that apoptotic cells undergoing secondary necrosis but not intact apoptotic cells provoked substantial immune responses, which were mediated through the toll-like receptor 2 (TLR2) pathway. The d...

CD28/CD154 blockade prevention of autoimmune diabetes CD28/CD154 blockade prevents autoimmune diabetes by inducing non-deletional tolerance following effector T cell inhibition and regulatory T cell expansion

Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity

BACKGROUND Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet β cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell-mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-o...

T-cell Tolerance Following Bacterial Glutamic Acid Decarboxylase (GAD) Feeding in Streptozotocin-induced Diabetes

Background: Autoimmune type 1 diabetes mellitus is caused by T-cell mediated immune destruction of the insulin-producing β-cell in pancreatic islets of Langerhans. Specificity of the auto-antibodies and of the auto-reactive T-cells has been investigated, in which several auto-antigens were proposed. Objective: To determine whether glutamic acid decarboxylase (GAD) feeding would induce oral tol...