Immortalization of human CD8(+) T cell clones by ectopic expression of telomerase reverse transcriptase

Replicative senescence of T cells is correlated with erosion of telomere en ds. Telomerase plays a key role in maintaining telomere length. Therefore, it is thought that telomerase regulates the life span of T cells. To test t his hypothesis, we have over-expressed human telomerase reverse transcripta se in human CD8(+) T cells. Ectopic expression of human telomerase reverse transcriptase led to immortalization of these T cells, without altering the phenotype and without loss of specificity or functionality. As the T cells remained dependent on cytokines and Ag stimulation for their in vitro expa nsion, we conclude that immortalization was achieved without malignant tran sformation.