In vivo ligation of CD3 on neonatal scid thymocytes blocks γ-irradiation-induced TCRβ rearrangements and thymic lymphomagenesis

Cherie Martina, Jay Wayne, Anthony Bell, Yung Chang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Several studies have shown that the developmental arrest of severe combined immune deficiency (scid) thymocytes during the CD4-CD8- double negative (DN) to CD4+CD8+ double positive (DP) transition can be overcome by a sub-lethal dose of ionizing radiation (IR). Concurrent with this developmental progression, IR also induces variable (diversity) joining (V(D)J) recombination at T cell receptor (TCR), δ, β, and γ, but not α loci. In addition, all irradiated scid mice succumb to thymic lymphoma. In this study, we demonstrate that scid neonates treated with anti-CD3ε antibody become more resistant to the development of thymoma upon exposure to IR. It is known that the anti-CD3ε antibody treatment induces T cell progression to the DP stage bypassing TCRβ rearrangement. We show here that the resistance to tumor development is correlated with a reduction of TCRβ rearrangements that are induced by IR. However, TCRγ rearrangements were not altered by the antibody treatment. The particular effect of anti-CD3ε antibody on TCRβ rearrangements is likely attributed to a decline of the double negative thymocyte subset (DN3), in which TCRβ rearrangements predominantly occur. These results suggest that the developmental stage of scid thymocytes can influence the effect of IR on TCR rearrangements as well as lymphomagenesis.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalImmunology Letters
Volume85
Issue number3
DOIs
StatePublished - Feb 3 2003

Keywords

  • Ionizing radiation
  • Scid
  • T cell development
  • Thymus
  • V(D)J recombination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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