Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function

被引:18
作者
Andersen, Hanne
Barsov, Eugene V.
Trivett, Matthew T.
Trubey, Charles M.
Giavedoni, Luis D.
Lifson, Jeffrey D.
Ott, David E.
Ohlen, Claes
机构
[1] NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA
[2] SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78284 USA
关键词
D O I
10.1089/aid.2006.0194
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell lines and clones play a key role in basic studies of cellular immunology, and are also finding applications in adoptive immunotherapy. However, with proliferative expansion, T cells ultimately undergo cellular senescence and death, so that long-term culture of T cell clones is difficult to achieve. Expression of telomerase reverse transcriptase (TERT) in differentiated cells can maintain telomere length over many cell divisions, preventing senescence. We used a retroviral vector that expresses the human TERT (hTERT) gene to transduce a rhesus macaque-derived CD8(+) T cell clone specific for the MamuA*01-restricted immunodominant SIV gag epitope CM9. Extensive in vitro characterization revealed that the untransduced parental cells and the hTERT-transduced cells displayed comparable proliferation capacity, effector memory surface marker profiles, cytolytic activities, and cytokine profiles following antigen stimulation. The hTERT-transduced cells showed improved survival compared to parallel nontransduced cultures during in vitro propagation in longterm culture. Such immortalized T cells may be useful as a source of consistent controls for in vitro assays of cellular immune function, and as a potentially important reagent for autologous adoptive cellular immunotherapy studies in macaques.
引用
收藏
页码:456 / 465
页数:10
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