Immortalization of Human and Rhesus Macaque Primary Antigen‐Specific T Cells by Retrovirally Transduced Telomerase Reverse Transcriptase

Human and rhesus macaque primary antigen-specific T cells derived from infected or immunized individuals or animals are a valuable material with which to study cellular immune responses against pathogens and tumors. Antigen-specific T cells can be expanded in vitro but have a finite proliferative life span. After a limited period in culture, primary T cells undergo replicative senescence and stop dividing. This restricts their applicability to short-term experiments and complicates their use in adoptive immunotherapy. The proliferative life span of primary human and rhesus macaque T cells can be considerably extended by ectopically expressed human telomerase reverse transcriptase (TERT). Antigen-specific T cells transduced with TERT-expressing retroviral vectors can proliferate and expand in culture for long periods of time while maintaining their primary T cell characteristics, including antigen-specific responses. Thus, TERT-immortalized T cells are an important and valuable resource for studying T cell-mediated immune responses and, potentially, for adoptive immunotherapy.