Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells

Recent experiments have suggested that tumor necrosis factor α (TNFα) can down-regulate islet-specific T cells and prevent the development of autoimmune diabetes. Here we demonstrate that transgenic mice expressing both TNFα and the Leishmania major LACK antigen in the pancreas (RIP-TNFα/RIP- LACK) exhibit an impaired ability to mount a CD4⁺ T cell response against LACK. In addition, peripheral CD4⁺ T cells from TCR transgenic mice (TCR- LACK/RIP-TNFα/RIP-LACK) produced reduced interleukin-2 but elevated levels of T helper 2 cytokines in response to LACK peptide in vitro. Taken together, our data suggest that TNFα may act in vivo to modulate a potentially damaging self-reactive T cell response by inducing tolerance to pancreatic antigens.