Bystander suppression in an auto-immune disease model

Excerpt

Autoreactive regulatory T cells, which are capable of preventing autoimmune disease, have been described in several animal models. If the specificity of the regulatory lymphocytes differs from that of the autoaggressive lymphocytes, the phenomenon has been termed bystander suppression. This paper investigates the mechanism of bystander suppression using a murine model of type 1 diabetes. These mice express the transgene encoding the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP). The NP is therefore selectively expressed in the ? cells of the pancreatic islets of Langerhans, and infection of these mice with LCMV results in progressive destruction of ? islet cells, leading to overt type 1 diabetes. The authors have previously shown that oral insulin can prevent diabetes in these mice. Here they demonstrate the presence of insulin-specific regulatory T cells. These cells locally suppress the destructive T cell responses directed against the viral NP, which is expressed from the transgene on ? islet cells. This regulatory mechanism was dependent on the secretion of IL-4 and on the presence of the IL-4 signalling component, stat6. To characterize regulatory autoreactive T cells and to investigate a potential mechanism of bystander suppression. …