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

Aida Gabdoulkhakova, Gunnel Henriksson, Nadezhda Avkhacheva, Alexander Sofin, Anders Bredberg

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

7 Citeringar (SciVal)
137 Nedladdningar (Pure)

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)135-143
TidskriftImmunogenetics
Volym59
Utgåva2
DOI
StatusPublished - 2007

Ämnesklassifikation (UKÄ)

  • Mikrobiologi inom det medicinska området

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