Programmed death of autoreactive thymocytes - PubMed (original) (raw)
. 1990 Feb 15;343(6259):642-4.
doi: 10.1038/343642a0.
Affiliations
- PMID: 2304535
- DOI: 10.1038/343642a0
Programmed death of autoreactive thymocytes
H R MacDonald et al. Nature. 1990.
Abstract
T lymphocytes bearing high-affinity T-cell receptors (TCR) for self-antigens are clonally deleted during thymus development. Several recent studies have identified variable domains of the beta-chain of the TCR that are specifically deleted in vivo in mouse strains that express major histocompatibility complex class II molecules in addition to poorly defined self-antigens, including those encoded by the Mls-1a and Mls-2a loci. Deletion of autoreactive cells in these systems occurs in the thymus, and antibody blocking experiments in vivo have implicated the phenotypically immature CD4+CD8+ 'cortical' subset as the target population for clonal deletion. Similarly, studies with transgenic mice bearing autoreactive TCR have provided independent evidence that clonal deletion occurs at the CD4+CD8+ stage of development. But none of these studies directly identified dying autoreactive cells, and the circumstances leading to deletion remain unclear. Here we report that neonatal thymus contains a significant population of phenotypically mature CD4+CD8- cells bearing autoreactive TCR. When placed in short-term culture, a large proportion (60%) of these autoreactive cells die selectively. Furthermore, their death can be prevented by inhibitors of macromolecule (RNA and protein) synthesis, as is the case for glucocorticoid-induced death of thymocytes. These data indicate that physiological clonal deletion of autoreactive cells involves 'programmed' cell death, and that it can occur in cells with a mature (CD4+CD8-) surface phenotype.
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