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Cell growth and gene rearrangement signals during the development of T lymphocytes within the thymus.

Authors
  • Owen, J J
  • Jenkinson, E J
  • Kingston, R
  • Williams, G T
  • Smith, C A
Type
Published Article
Journal
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Publication Date
Mar 12, 1990
Volume
327
Issue
1239
Pages
111–116
Identifiers
PMID: 1969652
Source
Medline
License
Unknown

Abstract

The thymus provides signals that control the proliferation and differentiation of T lymphocytes and select the repertoire of T-cell specificities. Antibodies to CD3 molecules inhibit full rearrangement of T-cell receptor beta chain genes in organ cultures of early embryo mouse thymus. Whether this effect is mediated through gamma delta CD3 expressing cells, which are present in small numbers at this stage, or through low amounts of CD3 on alpha beta precursor cells is unclear. A requirement for special gene rearrangement signals within the thymus is supported also by the observations that growth factors such as IL-2 and IL-4, although stimulating proliferation of precursor cells removed from the thymus, do not induce full T-cell receptor gene rearrangements. Recent studies show that newly formed thymic lymphocytes expressing alpha beta CD3 receptors are targets for negative selection (deletion) as a means of removing autoreactive cells. Signalling to immature thymocytes via the alpha beta CD3 complex induces the activation of endogenous endonucleases that cleave DNA into oligonucleosomal fragments. We suggest that the activation of this mechanism is the means by which autoreactive cells are removed.

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