1. Impaired fetal thymocyte development after efficient adenovirus-mediated inhibition of NF-kappa B activation.
- Author
-
Bakker TR, Renno T, and Jongeneel CV
- Subjects
- Adenoviridae immunology, Animals, Apoptosis genetics, Apoptosis immunology, Cell Division genetics, Cell Division immunology, Cell Line, DNA-Binding Proteins genetics, Humans, Hyaluronan Receptors biosynthesis, Hyaluronan Receptors genetics, I-kappa B Proteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Receptors, Antigen, T-Cell, alpha-beta biosynthesis, Receptors, Interleukin-2 biosynthesis, Receptors, Interleukin-2 genetics, T-Lymphocytes metabolism, T-Lymphocytes virology, Thymus Gland metabolism, Thymus Gland virology, Transfection immunology, Adenoviridae genetics, Embryonic and Fetal Development genetics, Embryonic and Fetal Development immunology, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, T-Lymphocytes pathology, Thymus Gland pathology
- 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-kappa B inhibitor I kappa B alpha (mut-I kappa B) and to study the maturation defects occurring when NF-kappa B activation is inhibited during fetal development. Fetal thymocytes infected with adenovirus containing mut-I kappa B 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 beta-chain. However, apoptosis was much higher in FTOC infected with adenovirus containing mut-I kappa B than in FTOC infected with a control virus. Taken together, these results suggest that NF-kappa B plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development.
- Published
- 1999