Autoantibodies Help T Cells 'See' Their Target

In a new study in the Journal of Clinical Investigation, Raphael Clynes and colleagues from Columbia University show that autoantibodies are required to induce disease in a mouse model of autoimmune diabetes mediated by immune cells known as T cells. When CD8+ T cells that recognize ovalbumin were transplanted into mice expressing ovalbumin in the pancreas (the organ targeted by the immune system in type I diabetes) they caused diabetes only if the mice were also transplanted with IgG antibodies that recognize ovalbumin.

The antibodies were shown to enable immune cells known as dendritic cells to take up dying pancreatic cells expressing ovalbumin and present the ovalbumin to CD8+ T cells (a process known as cross-presentation) in a form that they could "see". Cross-presentation required that the dendritic cells express activating IgG1 receptors.

Because ovalbumin-specific antibodies were required for the activation of disease-causing T cells the authors suggest that developing approaches to prevent autoantibodies from enabling dendritic cells to cross-present self antigen to T cells might provide a new approach to treat autoimmune diseases.

Article: Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance