Premium
5‐Fluorouracil enhances apoptosis sensitivity of T lymphocytes mediated by CD3ε
Author(s) -
Cheng Hong,
Liu Yanxin,
Liu Shilian,
Zheng Dexian
Publication year - 2004
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1083
Subject(s) - jurkat cells , cd8 , apoptosis , cd3 , cytotoxic t cell , t cell receptor , microbiology and biotechnology , t cell , biology , programmed cell death , antibody , cancer research , chemistry , antigen , immunology , immune system , biochemistry , in vitro
Previous studies by our laboratory have reported that the T cell receptor (TCR) TCR/CD3 complex could mediate activation as well as apoptosis of T lymphocytes. Two tyrosine residues in the ITAM (immuno‐receptor tyrosine‐based activation motifs) of CD3ε were required for apoptosis signalling of Jurkat T lymphocytes. Stable cell lines TJK and T3JK produced from CD8 − Jurkat T lymphocytes by transfection with wild‐type and mutant CD8ε (fusion of the extracellular and transmembrane domains of human CD8α to the intracellular domain of mouse CD3ε), were used with CD8 − Jurkat T lymphocytes for studying the role of single intact CD3ε. 5‐Fluorouracil (5‐FU), a chemotherapeutic drug can induce cell death of many tumour cell lines. In the present experiments, we examined the expression of caspase‐3, p53 and Bid in the three cell lines induced by 5‐FU and/or anti‐CD8 antibody. We found high expression of p53 during activation‐induced cell death of TJK cells mediated by anti‐CD8 antibody and apoptosis of TJK and T3JK induced by 5‐FU, implicating p53 involvement in apoptosis of leukemia cells induced by anti‐CD8 antibody and 5‐FU. We also detected the active form of caspase‐3 and Bid in apoptotic leukemia cells after treatment with 5‐FU and/or anti‐CD8 antibody, indicating that the drug and antibody induced cell death through caspase‐3 and the signal pathway may involve the Bcl‐2 protein family. Our results showed that combined treatment with 5‐FU and anti‐CD8 antibody could enhance the rate of apoptosis induced by 5‐FU or anti‐CD8 antibody through increased expression of p53 and by promoting activation of caspase‐3 and Bid. This suggests that the combination of 5‐FU and anti‐CD8 antibody may play an important role in inducing apoptosis of leukemia cells. Copyright © 2004 John Wiley & Sons, Ltd.