Perforin/Fas-ligand double deficiency is associated with macrophage expansion and severe pancreatitis

Julie Spielman, Richard K. Lee, Eckhard R Podack

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

We report that perforin/Fas-ligand double-deficient mice die early of severe pancreatitis. Female mice, in addition, are infertile and suffer from hysterosalpingitis. Tissue destruction is accompanied by infiltration with Mac-1 (CD11b)-positive monocytes/macrophages, Mac-1-positive T cells, and expansion of CD8+ T cells. In vivo inactivation of monocytes/macrophages by carrageenan reverses disease progression and restores fertility of female mice. Perforin/Fas-ligand double-deficient CD4+ or CD8+ CTL are unable to lyse cognate-activated macrophages, and therefore are unable to mediate negative feedback regulation by lysis of APCs, thereby preventing further T cell activation. These studies demonstrate a novel role for perforin in homeostatic regulation of the immune response.

Original languageEnglish (US)
Pages (from-to)7063-7070
Number of pages8
JournalJournal of Immunology
Volume161
Issue number12
StatePublished - Dec 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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