Abstract
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 long-term culture. Such immortalised 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 456-465 |
| Number of pages | 10 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 23 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Virology
Cite this
Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function. / Andersen, Hanne; Barsov, Eugene V.; Trivett, Matthew T.; Trubey, Charles M.; Giavedoni, Luis D.; Lifson, Jeffrey D.; Ott, David E.; Öhlén, Claes.
In: AIDS Research and Human Retroviruses, Vol. 23, No. 3, 03.2007, p. 456-465.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function
AU - Andersen, Hanne
AU - Barsov, Eugene V.
AU - Trivett, Matthew T.
AU - Trubey, Charles M.
AU - Giavedoni, Luis D.
AU - Lifson, Jeffrey D.
AU - Ott, David E.
AU - Öhlén, Claes
PY - 2007/3
Y1 - 2007/3
N2 - 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 long-term culture. Such immortalised 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.
AB - 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 long-term culture. Such immortalised 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.
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U2 - 10.1089/aid.2006.0194
DO - 10.1089/aid.2006.0194
M3 - Article
VL - 23
SP - 456
EP - 465
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 3
ER -