Negative selection of thymocytes. A novel polymerase chain reaction-based molecular analysis detects requirements for macromolecular synthesis
D'Adamio, L.; Clayton, L.K.; Awad, K.M.; Reinherz, E.L.
Journal of Immunology 149(11): 3550-3553
1992
ISSN/ISBN: 0022-1767 PMID: 1331238 Document Number: 405077
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.