Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function.
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 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.
Andersen
Hanne
H
AIDS Vaccine Program, SAIC-Frederick/NCI-Frederick, Frederick, Maryland 21702, USA.
Barsov
Eugene V
EV
Trivett
Matthew T
MT
Trubey
Charles M
CM
Giavedoni
Luis D
LD
Lifson
Jeffrey D
JD
Ott
David E
DE
Ohlén
Claes
C
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism* / Q000821:virology; D019098:Telomerase / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*
C509186:TERT protein, human; D019098:Telomerase