Programmed death of autoreactive thymocytes (original) (raw)

Nature volume 343, pages 642–644 (1990)Cite this article

Abstract

T LYMPHOCYTES bearing high-affinity T-cell receptors (TCR) for self-antigens are clonally deleted during thymus development1. Several recent studies1,4–10have identified variable domains of the β-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-1 a Mls-2 a 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 deletion11,12. Similarly, studies with transgenic mice bearing autoreactive TCR have provided independent evidence that clonal deletion occurs at the CD4+CD8+ stage of development13. 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 popula- tion 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 thymocytes2,3. 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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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, 1066, Epalinges, Switzerland
    H. Robson MacDonald & Rosemary K. Lees

Authors

  1. H. Robson MacDonald
  2. Rosemary K. Lees

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MacDonald, H., Lees, R. Programmed death of autoreactive thymocytes.Nature 343, 642–644 (1990). https://doi.org/10.1038/343642a0

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