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

Gabdoulkhakova, Aida LU ; Henriksson, Gunnel LU ; Avkhacheva, Nadezhda ; Sofin, Alexander and Bredberg, Anders LU (2007) In Immunogenetics 59(2). p.135-143
Abstract
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... (More)
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. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
T-cell activation, gene inactivation, PIG-A, HPRT, DNA methylation
in
Immunogenetics
volume
59
issue
2
pages
135 - 143
publisher
Springer
external identifiers
  • wos:000243556900004
  • scopus:33846387460
ISSN
1432-1211
DOI
10.1007/s00251-006-0180-8
language
English
LU publication?
yes
id
eced348c-a302-4df4-a81d-cb6f39951877 (old id 163828)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17180623&dopt=Abstract
date added to LUP
2016-04-01 16:46:14
date last changed
2022-01-28 22:01:22
@article{eced348c-a302-4df4-a81d-cb6f39951877,
  abstract     = {{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.}},
  author       = {{Gabdoulkhakova, Aida and Henriksson, Gunnel and Avkhacheva, Nadezhda and Sofin, Alexander and Bredberg, Anders}},
  issn         = {{1432-1211}},
  keywords     = {{T-cell activation; gene inactivation; PIG-A; HPRT; DNA methylation}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{135--143}},
  publisher    = {{Springer}},
  series       = {{Immunogenetics}},
  title        = {{High rate of mutation reporter gene inactivation during human T cell proliferation.}},
  url          = {{https://lup.lub.lu.se/search/files/4775203/625798.pdf}},
  doi          = {{10.1007/s00251-006-0180-8}},
  volume       = {{59}},
  year         = {{2007}},
}