Immunological tolerance to a pancreatic antigen as a result of local expression of TNF alpha by islet beta cells

Recent experiments have suggested that tumor necrosis factor alpha (TNF alpha) can down-regulate islet-specific T cells and prevent the development of autoimmune diabetes. Here we demonstrate that transgenic mice expressing both TNF alpha and the Leishmania major LACK antigen in the pancreas (RIP-TNF alpha/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-TNF alpha/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 TNF alpha may act in vivo to modulate a potentially damaging self-reactive T cell response by inducing tolerance to pancreatic antigens.