The role of TNF-TNFR2 interactions in generation of CTL responses and clearance of hepatic adenovirus infection

Michel I. Kafrouni, Geri Brown, Dwain L Thiele

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Deficiency or inhibition of tumor necrosis factor (TNF) significantly prolongs hepatic expression of recombinant adenoviral vectors. To explore mechanisms responsible for this observation, the present studies examined the effects of TNF versus TNF receptor 1 (TNFR1) or TNFR2 deficiency on the course of antiviral-immune responses to a replication-deficient, β -galactosidase-encoding recombinant adenovirus (AdCMV-lacZ). Clearance of AdCMV-lacZ was significantly delayed in TNF-deficient mice. Less pronounced but significant delays in AdCMV-lacZ clearance were observed in TNFR2-deficient but not TNFR1-deficient mice. Numbers of interferon-γ expressing intrahepatic lymphocytes (IHL) were similar in Ad-CMV-lacZ-infected, TNF-deficient, TNFR1-deficient, TNFR2-deficient, and control mice. However, IHL isolated from AdCMV-lacZ-infected, TNF-deficient or AdCMV-lacZ-infected, TNFR2-deficient mice exhibited decreased levels of FasL expression and adenovirus-specific cytolytic T lymphocyte (CTL) activity. Similar defects in allo-specific killing of Fas-sensitive hepatocyte targets by TNF-deficient or TNFR2-deficient but not TNFR1-deficient CTL were also noted. No defects in generation of allo-specific cytotoxicity directed against perforin-sensitive target cells were noted in TNF-, TNFR1-, or TNFR2-deficient lymphocytes. These findings indicate that TNF/TNFR2 interactions facilitate generation of FasL-dependent CTL effector pathways that play an important role in in vivo antiviral-immune responses in the liver.

Original languageEnglish (US)
Pages (from-to)564-571
Number of pages8
JournalJournal of Leukocyte Biology
Volume74
Issue number4
DOIs
StatePublished - Oct 2003

Keywords

  • Cytokine receptors
  • Cytokines
  • Cytotoxicity
  • Viral

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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