Impaired fetal thymocyte development after efficient adenovirus-mediated inhibition of NF-κB activation

Talitha R. Bakker, Toufic Renno, C. Victor Jongeneel

Research output: Contribution to journalArticlepeer-review

Abstract

We introduce a new experimental system combining adenovirus-mediated gene transfer and fetal thymic organ culture (FTOC). This system allowed us to efficiently express in developing thymocytes a mutant form of the NF-κB inhibitor IκBα (mut-IκB) and to study the maturation defects occurring when NF-κB activation is inhibited during fetal development. Fetal thymocytes infected with adenovirus containing mut-IκB were found to develop normally until the CD44-CD25+, CD4-CD8- double-negative stage, while production of more mature double-positive and single-positive populations was strongly decreased. Proliferation, as measured by the percentage of cells in cycle appeared normal, as did rearrangement and expression of the TCR β- chain. However, apoptosis was much higher in FTOC infected with adenovirus containing mut-IκB than in FTOC infected with a control virus. Taken together, these results suggest that NF-κB plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development.

Original languageEnglish (US)
Pages (from-to)3456-3462
Number of pages7
JournalJournal of Immunology
Volume162
Issue number6
StatePublished - Mar 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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