Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction

Myung Shik Lee, Lise Wogensen, Judith Shizuru, Michael B.A. Oldstone, Nora Sarvetnick

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

IL-10 inhibits macrophage-dependent antigen presentation, cytokine production, and generation of allospecific cells in vitro. These findings have lead to the widespread expectation that IL-10 may be a useful immunosuppressive agent to inhibit allograft rejection or autoimmunity in vivo. We used two experimental paradigms to study effects of murine IL-10 on in vivo immune responses. First, fetal pancreata or adult pancreatic islets from transgenic mice expressing IL-10 in pancreatic β cells (Ins-IL-10 mice) were grafted across the MHC barrier to examine if IL-10 could inhibit allograft rejection. Second, Ins-IL-10 mice were crossed with transgenic mice expressing lymphocytic choriomeningitis virus (LCMV) antigens in pancreatic β cells. These mice were infected with LCMV to elicit autoimmune diabetes, allowing us to ask if IL-10 protects islets from autoimmune destruction. We observed that allografts from IL-10-transgenic donors were rejected with comparable kinetics to the rejection of control nontransgenic allografts, indicating that IL-10 does not inhibit allograft rejection. After LCMV infection, IL-10 and LCMV antigen double transgenic mice developed diabetes earlier than LCMV antigen single transgenic littermates, suggesting that IL- 10 does not inhibit islet antigen presentation or recognition. Our results contrast to in vitro observations and suggest that IL-10 cannot overcome immune-mediated tissue destruction within the pancreas.

Original languageEnglish (US)
Pages (from-to)1332-1338
Number of pages7
JournalJournal of Clinical Investigation
Volume93
Issue number3
DOIs
StatePublished - Mar 1994

Keywords

  • allograft
  • autoimmunity
  • diabetes mellitus
  • transgenic mice
  • viral infection

ASJC Scopus subject areas

  • Medicine(all)

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