Lymphocytes from autoimmune MRL lpr/lpr mice are hyperresponsive to IL-18 and overexpress the IL-18 receptor accessory chain

D. Neumann, E. Del Giudice, A. Ciaramella, D. Boraschi, P. Bossù

Research output: Contribution to journalArticlepeer-review

Abstract

MRL lpr/lpr mice spontaneously develop a severe autoimmune lupus syndrome characterized by strong autoantibody production and massive lymphoproliferation, in which IFN-γ plays a major pathogenic effect. The role of the IFN-γ-inducing cytokine IL-18 in the autoimmune syndrome of lpr/lpr mice has been investigated. In response to IL-18, lymph node cells of lpr/lpr mice produce significant amounts of IFN-γ, and proliferate more potently as compared with cells from +/+ mice. Cells likely responsible for such hyperresponsiveness to IL-18 include NK cells and the CD4+/CD8+ self-reactive T lymphocytes characteristically present in lymph nodes of lpr/lpr mice. Analysis of the expression of IL-18r complex revealed that mrna for the IL-18Rα-chain is constitutively expressed at similar level both in +/+ and lpr/lpr lymphocytes. In contrast, the expression of the accessory receptor chain IL-18rβ is low in unstimulated +/+ cells but significantly high in lpr/lpr cells. Thus, the abnormally high expression of the IL-18R chain IL-18Rβ could be one of the causes of the hyperresponsiveness of lpr/lpr cells to IL-18 at the basis of consequent enhancement of IFN-γ production and development of IFN-γ-dependent autoimmune pathology.

Original languageEnglish
Pages (from-to)3757-3762
Number of pages6
JournalJournal of Immunology
Volume166
Issue number6
Publication statusPublished - Mar 15 2001

ASJC Scopus subject areas

  • Immunology

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