TY - JOUR
T1 - Ectopic hTERT expression extends the life span of human CD4(+) helper and regulatory T-cell clones and confers resistance to oxidative stress-induced apoptosis
AU - Luiten, Rosalie M.
AU - Péne, Jérome
AU - Yssel, Hans
AU - Spits, Hergen
PY - 2003
Y1 - 2003
N2 - Human somatic cells have a limited life span in vitro. Upon aging and with each cell division, shortening of telomeres occurs, which eventually will lead to cell cycle arrest. Ectopic hTERT expression has been shown to extend the life span of human T cells by preventing this telomere erosion. In the present study, we have shown that ectopic hTERT expression extends the life span of CD4(+) T helper type 1 or 2 and,regulatory T-cell clones and affected neither the in vitro cytokine production profile. nor their specificity for antigen. In mixed cell cultures, ectopic hTERT-expressing clones were found to expand in greater numbers than untransduced cells of the same replicative age. This ectopic hTERT-induced growth ad vantage was not due to an enhanced cell division rate or number of divisions following, T-cell receptor-mediated activation, as determined in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling experiments. Moreover, the susceptibility to activation-induced cell death of both cell types was similar. However, cultures of resting hTERT-transduced T cells contained higher frequencies of Bcl-2-expressing cells and lower active caspase-3-expressing cells, compared with wild-type cells. Furthermore, hTERT-transduced cells were more resistant to oxidative stress, which causes preferential DNA damage in telomeres. Taken together, these results show that ectopic hTERT expression not only protects proliferating T cells from replicative senescence but also confers resistance to apoptosis induced by oxidative stress. (C) 2003 by The American Society of Hematology
AB - Human somatic cells have a limited life span in vitro. Upon aging and with each cell division, shortening of telomeres occurs, which eventually will lead to cell cycle arrest. Ectopic hTERT expression has been shown to extend the life span of human T cells by preventing this telomere erosion. In the present study, we have shown that ectopic hTERT expression extends the life span of CD4(+) T helper type 1 or 2 and,regulatory T-cell clones and affected neither the in vitro cytokine production profile. nor their specificity for antigen. In mixed cell cultures, ectopic hTERT-expressing clones were found to expand in greater numbers than untransduced cells of the same replicative age. This ectopic hTERT-induced growth ad vantage was not due to an enhanced cell division rate or number of divisions following, T-cell receptor-mediated activation, as determined in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling experiments. Moreover, the susceptibility to activation-induced cell death of both cell types was similar. However, cultures of resting hTERT-transduced T cells contained higher frequencies of Bcl-2-expressing cells and lower active caspase-3-expressing cells, compared with wild-type cells. Furthermore, hTERT-transduced cells were more resistant to oxidative stress, which causes preferential DNA damage in telomeres. Taken together, these results show that ectopic hTERT expression not only protects proliferating T cells from replicative senescence but also confers resistance to apoptosis induced by oxidative stress. (C) 2003 by The American Society of Hematology
U2 - https://doi.org/10.1182/blood-2002-07-2018
DO - https://doi.org/10.1182/blood-2002-07-2018
M3 - Article
C2 - 12586632
SN - 0006-4971
VL - 101
SP - 4512
EP - 4519
JO - Blood
JF - Blood
IS - 11
ER -