In addition to its biochemical functions, insulin can play an immunological role, acting as an autoantigen in human type I diabetes. In the NOD mouse model, many islet-reactive T cells invading the islet are insulin-specific. Studies suggest that insulin is also capable of generating a diabetes-protective immune response.
A regulatory/immunosuppressive T cell line (designated 2H6) was isolated from the pancreatic lymph nodes of a diabetic NOD mouse. These cells specifically recognize the insulin β chain peptide 12-25 or 9-23, secrete IFNG and TGFB, and have the ability to block both the adoptive transfer of diabetes in NOD-scid recipients and the spontaneous development of diabetes in NOD mice.
Based on this cell line, a transgenic strain that expresses the autoreactive 2H6 Vα6/Vβ14 regulatory T cell receptor was created on the NOD genetic background. Expression of the transgene blocks CD8+ T cell development. These mice are completely protected from diabetes development and upon binding express significant amounts of IFNG and TGFB. Cells from these mice can differentiate into potent regulatory cells that can protect NOD mice from the aggressive effects of spleen cells transferred from diabetic mice and diabetogenic cells from BDC2.5 transgenic mice.
No phenotypic differences between hemizygotes and homozygotes have been found.
This strain has been useful in studies of regulatory T cell (Treg) function and in the development of therapies for autoimmune disorders.
