Autoimmune insulitis and diabetes in the absence of antigen-specific contact between T cells and β-islet cells

Abstract

Autoimmune diabetes develops following recognition of organ‐specific antigens by T cells. The disease begins with peri‐islet infiltration by mononuclear cells, proceeds with insulitis and becomes manifest with destruction of insulin‐producing islet β‐cells. T cells are necessary to induce insulitis and diabetes, but it is not clear by what mechanisms they can do so, i.  e. whether the T cells need to make antigen‐specific contact with the β‐cell or whether other interactions are sufficient to induce β‐cell death. In the present study we have constructed chimeric mice in which the bone marrow‐derived antigen‐presenting cells, but not the islet β‐cells, are capable of presenting antigen to monospecific T cells. We show that both insulitis as well as β‐cell destruction can proceed in the absence of islet β‐cell surface antigen recognition by T cells. Our results support the notion that diabetes can be caused by distinct effector mechanisms.