TY - JOUR
T1 - Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells
AU - Mcsorley, Stephen J
AU - Soldera, Sylvelie
AU - Malherbe, Laurent
AU - Carnaud, Claude
AU - Locksley, Richard M.
AU - Flaveil, Richard A.
AU - Glaichenhaus, Nicolas
PY - 1997/9
Y1 - 1997/9
N2 - 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.
AB - 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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U2 - 10.1016/S1074-7613(00)80361-1
DO - 10.1016/S1074-7613(00)80361-1
M3 - Article
C2 - 9324360
AN - SCOPUS:0030815504
VL - 7
SP - 401
EP - 409
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -