Transduction with Human Telomerase Reverse Transcriptase Immortalizes A Rhesus Macaque CD8+T Cell Clone with Maintenance of Surface Marker Phenotype And Function
- 1 March 2007
- journal article
- Published by Mary Ann Liebert Inc in AIDS Research and Human Retroviruses
- Vol. 23 (3), 456-465
- https://doi.org/10.1089/aid.2006.0194
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 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.Keywords
This publication has 43 references indexed in Scilit:
- Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239Journal of Virology, 2006
- Capture of antigen-specific T lymphocytes from human blood by selective immortalization to establish long-term T-cell lines maintaining primary cell characteristicsImmunology Letters, 2006
- Genomic stability and functional activity may be lost in telomerase-transduced human CD8+ T lymphocytesBlood, 2005
- Effect of CD8 + Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus MacaquesJournal of Virology, 2005
- Understanding the generation and function of memory T cell subsetsCurrent Opinion in Immunology, 2005
- Telomerase levels control the lifespan of human T lymphocytesBlood, 2003
- Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunityNature, 2002
- Control of a Mucosal Challenge and Prevention of AIDS by a Multiprotein DNA/MVA VaccineScience, 2001
- Nonmyeloablative Immunosuppressive Regimen Prolongs In Vivo Persistence of Gene-Modified Autologous T Cells in a Nonhuman Primate ModelJournal of Virology, 2001
- Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoformsEuropean Journal of Immunology, 1999