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

Stephen J Mcsorley, Sylvelie Soldera, Laurent Malherbe, Claude Carnaud, Richard M. Locksley, Richard A. Flaveil, Nicolas Glaichenhaus

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)401-409
Number of pages9
JournalImmunity
Volume7
Issue number3
DOIs
StatePublished - Sep 1997
Externally publishedYes

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Islets of Langerhans
Tumor Necrosis Factor-alpha
Antigens
T-Lymphocytes
Transgenic Mice
Leishmania major
Type 1 Diabetes Mellitus
Interleukin-2
Pancreas
Down-Regulation
Cytokines
Peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Mcsorley, S. J., Soldera, S., Malherbe, L., Carnaud, C., Locksley, R. M., Flaveil, R. A., & Glaichenhaus, N. (1997). Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells. Immunity, 7(3), 401-409. https://doi.org/10.1016/S1074-7613(00)80361-1

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 journalArticle

Mcsorley, SJ, Soldera, S, Malherbe, L, Carnaud, C, Locksley, RM, Flaveil, RA & Glaichenhaus, N 1997, 'Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells', Immunity, vol. 7, no. 3, pp. 401-409. https://doi.org/10.1016/S1074-7613(00)80361-1
Mcsorley, Stephen J ; Soldera, Sylvelie ; Malherbe, Laurent ; Carnaud, Claude ; Locksley, Richard M. ; Flaveil, Richard A. ; Glaichenhaus, Nicolas. / Immunological tolerance to a pancreatic antigen as a result of local expression of TNFα by islet β cells. In: Immunity. 1997 ; Vol. 7, No. 3. pp. 401-409.
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