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. Curr. Protoc. Immunol. 95:7.21B.1‐7.21B.20. © 2011 by John Wiley & Sons, Inc.