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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 401-409 |
| Number of pages | 9 |
| Journal | Immunity |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells. / Mcsorley, Stephen J; Soldera, Sylvelie; Malherbe, Laurent; Carnaud, Claude; Locksley, Richard M.; Flaveil, Richard A.; Glaichenhaus, Nicolas.
In: Immunity, Vol. 7, No. 3, 09.1997, p. 401-409.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=0030815504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030815504&partnerID=8YFLogxK
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 -