Autoreactive CD4(+) T cells protect from autoimmune diabetes via bystandersuppression using the IL-4/stat6 pathway

Targeted immune regulation can be achieved by use of tissue-specific T cell s and offers the potential for organ-specific suppression of destructive au toimmune processes. Here, we report the generation and characterization of insulin B chain-specific "autoreactive" CD4(+) regulatory T cells that loca lly suppress diabetogenic T cell responses against an unrelated self-antige n (viral transgene) in a virus-induced model for type 1 diabetes. Interleuk in 4 (IL-4) is essential for prevention of diabetes since regulatory T cell s cannot be induced in the absence of IL-4 or stat6 (IL-4 signaling pathway ). Our observations demonstrate that autoreactive regulatory T cells can su ppress autoreactive destructive T cell activity of differential antigenic s pecificity locally in the pancreatic draining lymph node, probably via cyto kine-mediated modulation of antigen-presenting cells.