title: Immunological tolerance to a pancreatic antigen as a result of local expression of TNFalpha by islet beta cells.
abstract: Recent experiments have suggested that tumor necrosis factor alpha (TNFalpha) can down-regulate islet-specific T cells and prevent the development of autoimmune diabetes. Here we demonstrate that transgenic mice expressing both TNFalpha and the Leishmania major LACK antigen in the pancreas (RIP-TNFalpha/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-TNFalpha/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 TNFalpha may act in vivo to modulate a potentially damaging self-reactive T cell response by inducing tolerance to pancreatic antigens.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UPR411, Valbonne, France.
authors.forename: S J
authors.initials: SJ
authors.lastname: McSorley
authors.forename: S
authors.initials: S
authors.lastname: Soldera
authors.forename: L
authors.initials: L
authors.lastname: Malherbe
authors.forename: C
authors.initials: C
authors.lastname: Carnaud
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
authors.forename: N
authors.initials: N
authors.lastname: Glaichenhaus
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D010641:Phenotype; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; C093139:LACK antigen, Leishmania