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High rate of mutation reporter gene inactivation during human T cell proliferation.

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Author

Summary, in English

Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response factors occur during in vitro T-cell proliferation, and an increased frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been reported in conditions associated with in vivo T-cell proliferation. We have applied two human somatic cell mutation reporter assays, for the HPRT and phosphatidylinositol glycan class A (PIG-A) genes, to human T cells activated in vitro with anti-CD3 and anti-CD28. We demonstrate proliferation throughout 6 weeks of cultivation, and find that the frequency of variant cells phenotypically negative for HPRT and PIG-A, respectively, increases from 10(-5) up to 10(-3)-10(-2). We also report preliminary evidence for low-density CpG methylation in the HPRT promoter suggesting that epigenetic modification may contribute to this markedly heightened rate of gene inactivation.

Publishing year

2007

Language

English

Pages

135-143

Publication/Series

Immunogenetics

Volume

59

Issue

2

Document type

Journal article

Publisher

Springer

Topic

  • Microbiology in the medical area

Keywords

  • T-cell activation
  • gene inactivation
  • PIG-A
  • HPRT
  • DNA methylation

Status

Published

Research group

  • Clinical Microbiology, Malmö

ISBN/ISSN/Other

  • ISSN: 1432-1211