Novel function of perforin in control of lymphocyte regulatory function and proliferation

J. Spielman, R. K. Lee, Eckhard R Podack

Research output: Contribution to journalArticle

Abstract

Mice deficient in both primary effector pathways of lymphocyte mediated cytotoxicity (perform and Fas-ligand), were created by breeding homozygous perform knockout mice with gld/gld Fas-ligand deficient mice and screening the F2 generation for homozygous cytotoxk double deficiency (CDD). CDD mice were normal at birth but became moribund even under viral antigen free conditions at around 8 weeks and usually did not survive 16 weeks. Death occurred after progressive wasting and was characterized by lymphadenopathy and mononuclear cell infiltration, which was especially severe in the exocrine pancreas and the female reproductive tract. Male CDD mice are fertile, but females fail to reproduce. Littermates similarly homozygous for Fas-ligand deficiency but expressing a single copy of the perform gene were protected from early death, and exhibited less severe mononuclear cell infiltration. The marked difference in severity of disease between CDD mice and iJttermates expressing a single perform gene implies a role for perform in immune regulatory function and lyraphoproliferation.

Original languageEnglish (US)
Pages (from-to)A1488
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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