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

SJ McSorley, S Soldera, L Malherbe, C Carnaud… - Immunity, 1997 - cell.com
SJ McSorley, S Soldera, L Malherbe, C Carnaud, RM Locksley, RA Flavell, N Glaichenhaus
Immunity, 1997cell.com
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 …
Abstract
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.
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