[Synergetic role of CD3epsilon and 5-fluorouracil in T Lymphocyte apoptosis and P53 expression].
OBJECTIVE
To investigate the relationship between apoptosis induced by CD3epsilon and 5-fluorouracil (5-FU), and study the P53 expression in the apoptosis process provide a novel insight and useful information of the apoptosis signaling pathway induced by CD3epsilon and/or 5-FU, and an important implication for the treatment of T-lymphocyte leukemia.


METHODS
The viabilities of Jurkat T lymphocytes (JK), TJK [JK with over-expression of the CD8epsilon chimeria molecule] and T3JK [JK with over-expression of the CD8epsilon (Y170F/Y181F) mutation molecule] cells were cultured and treated with pre-coated anti-CD8 mAb (200 micro g/ml) and/or 5-FU (2.5 micro g/ml) were detected with MTS assay and the apoptosis percentages were calculated. Western blot was used to detect P53 expression. To confirm the role of P53 in 5-FU-treated T lymphocytes, pCMV-p53 plasmid with wild type or mutant p53 were co-transfected transiently with pEGFP-c1 into TJK and T3JK cells, respectively.


RESULTS
CD3epsilon or 5-FU induced apoptosis of TJK with increase of P53 expression. Co-treatment with CD3epsilon specific antibody and 5-FU elevated the apoptotic rates and P53 expression in TJK cells remarkably. The cells transfected with wild-type p53 exhibited more sensitivity to 5-FU than that transfected with mutant p53.


CONCLUSIONS
Co-treatment of CD3epsilon and 5-FU increases the apoptosis and p53 expression, suggesting that there is a synergetic role of CD3epsilon and 5-FU on T lymphocytes.
Cheng
Hong
H
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Liu
Yan-xin
YX
Zhang
Jin-chun
JC
Liu
Shi-lian
SL
Zheng
De-xian
DX
D017209:Apoptosis; D017252:CD3 Complex / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D017252:CD3 Complex; C115335:CD3E protein, human; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil