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• W1933829908 endingPage "5780" @default.
• W1933829908 startingPage "5770" @default.
• W1933829908 abstract "Abstract To investigate how CD8+ T cells interact with β cells and local inflammatory cells in islets, we have isolated CD8+ T cell clones from nonobese diabetic (NOD) spleen that recognize and destroy both islets and the NOD insulinoma cell line NIT-1. The clones destroyed NOD islets with pre-existing inflammation better than islets without signs of inflammation. Islets from NOD-scid mice were destroyed only poorly, but that could be improved by adding IL-7 to the assay. Anti-IFN-γ Abs inhibited destruction of infiltrated islets. Single islets were effective stimulators of IFN-γ production by cloned CD8+ T cells, which varied &gt;50-fold depending on the degree of islet infiltration. This effect of the islet mononuclear infiltrate could be mimicked by adding spleen cells to NIT-1 cells, which augmented IFN-γ production above the level stimulated by NIT-1 cells alone. The enhancing effect of spleen cells could be attributed to their macrophage subpopulation and was not MHC restricted, although recognition of islet Ag by cloned CD8+ T cells and subsequent islet destruction was restricted to islets expressing H-2Db molecules. An inhibitor of inducible NO synthase inhibited destruction of inflamed islets by cloned CD8+ T cells. We propose that macrophages in inflamed islets provide a form of bystander costimulation of β cell-specific CD8+ T cells. CD8+ T cells respond to Ag and costimulation by producing IFN-γ that activates macrophages. Activated macrophages facilitate islet destruction by CD8+ T cells through a NO synthesis-dependent pathway." @default.
• W1933829908 created "2016-06-24" @default.
• W1933829908 creator A5017620837 @default.
• W1933829908 creator A5052770357 @default.
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• W1933829908 date "1999-12-01" @default.
• W1933829908 modified "2023-10-17" @default.
• W1933829908 title "Role of Inflammatory Infiltrate in Activation and Effector Function of Cloned Islet Reactive Nonobese Diabetic CD8+ T Cells: Involvement of a Nitric Oxide-Dependent Pathway" @default.
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• W1933829908 doi "https://doi.org/10.4049/jimmunol.163.11.5770" @default.
• W1933829908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10570259" @default.
• W1933829908 hasPublicationYear "1999" @default.
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