1. Negative selection of thymocytes. A novel polymerase chain reaction-based molecular analysis detects requirements for macromolecular synthesis.
- Author
-
D'Adamio L, Clayton LK, Awad KM, and Reinherz EL
- Subjects
- Animals, Apoptosis drug effects, Base Sequence, Cycloheximide pharmacology, DNA Damage, Dactinomycin pharmacology, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Mice, Mice, Inbred Strains, Molecular Sequence Data, Oligodeoxyribonucleotides chemistry, Polymerase Chain Reaction, Staphylococcus aureus immunology, Antigens, Bacterial immunology, Enterotoxins immunology, Immune Tolerance, Receptors, Antigen, T-Cell, alpha-beta genetics
- Abstract
Self-tolerance is mainly established through clonal deletion of autoreactive T cells during thymic differentiation. The mechanisms by which deletion is achieved are poorly understood. Here we use a specific polymerase chain reaction-based system to characterize DNA fragmentation and show that after in vivo treatment of neonatal mice with staphylococcus enterotoxin B, selective apoptosis of V beta 8+ thymocytes occurs. This process precedes detectable deletion of V beta 8+ cells as determined by phenotypic analysis. Moreover, in vivo administration of cycloheximide and, to a lesser extent, actinomycin D, inhibits apoptosis of staphylococcus enterotoxin B specific thymocytes. Thus, macromolecular synthesis is a requirement for negative selection.
- Published
- 1992