Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase

J Immunol. 2000 Oct 15;165(8):4239-45. doi: 10.4049/jimmunol.165.8.4239.

Abstract

Replicative senescence of T cells is correlated with erosion of telomere ends. Telomerase plays a key role in maintaining telomere length. Therefore, it is thought that telomerase regulates the life span of T cells. To test this hypothesis, we have over-expressed human telomerase reverse transcriptase in human CD8(+) T cells. Ectopic expression of human telomerase reverse transcriptase led to immortalization of these T cells, without altering the phenotype and without loss of specificity or functionality. As the T cells remained dependent on cytokines and Ag stimulation for their in vitro expansion, we conclude that immortalization was achieved without malignant transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / physiology
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Culture Techniques / methods
  • Cell Line
  • Cell Line, Transformed / enzymology*
  • Cell Line, Transformed / immunology*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Clone Cells / enzymology
  • Clone Cells / immunology
  • Cytokines / physiology
  • DNA-Binding Proteins
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Enzyme Stability / genetics
  • Enzyme Stability / immunology
  • Epitopes, T-Lymphocyte / analysis
  • Epitopes, T-Lymphocyte / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Immunophenotyping
  • Interleukin-7 / biosynthesis
  • Interleukin-7 / genetics
  • Lymphocyte Activation / genetics*
  • Monophenol Monooxygenase / immunology
  • Protein Engineering / methods
  • RNA*
  • RNA, Messenger / biosynthesis
  • Telomerase / biosynthesis*
  • Telomerase / genetics*
  • Telomere / enzymology
  • Telomere / genetics
  • Transduction, Genetic
  • Tumor Cells, Cultured

Substances

  • Antigens
  • Cytokines
  • DNA-Binding Proteins
  • Epitopes, T-Lymphocyte
  • Interleukin-7
  • RNA, Messenger
  • telomerase RNA
  • RNA
  • Monophenol Monooxygenase
  • Telomerase