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Fas/APO‐1 (CD95)‐mediated cytotoxicity is responsible for the apoptotic cell death of leukaemic cells induced by interleukin‐2‐activated T cells
Author(s) -
Komada Yoshihiro,
Zhou YanWen,
Zhang XaoLi,
Chen TongXin,
Tanaka Shigeki,
Azuma Eiichi,
Sakurai Minoru
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.8742505.x
Subject(s) - cytotoxic t cell , fas receptor , apoptosis , microbiology and biotechnology , cytotoxicity , cd8 , biology , programmed cell death , cell culture , chemistry , cancer research , antigen , immunology , biochemistry , in vitro , genetics
Apoptotic cell death is induced by the cross‐linking of Fas/APO‐1 receptor (CD95) in acute myelogenous leukaemia (AML) cells. Since CD95 ligand (CD95L) is expressed on interleukin‐2 (IL‐2)‐activated T cells, we investigated the involvement of CD95‐CD95L pathway in T cell‐mediated cytotoxicity against AML cells. Activated CD8 + T cells could efficiently kill a parental CD95‐sensitive AML cell line, MML‐1 and, to a lesser extent, a CD95‐resistant clone, MML‐1R. Neither MML‐1 nor MML‐1R cells were killed by activated CD4 + T cells. The blocking monoclonal antibody (MoAb) against CD95, ZB4, caused a significant inhibition of T‐cell‐mediated cytotoxicity against MML‐1 cells, but not against MML‐1R cells. Interestingly, MML‐1 cells underwent the classic nuclear morphologic changes and DNA fragmentation characteristic of apoptosis when cultured with activated T cells. Enumeration of apoptotic and necrotic nuclei showed that both apoptosis and necrosis were induced in MML‐1 cells, whereas necrosis was exclusively observed in MML‐1R cells. Apoptosis of MML‐1 cells was completely blocked in the presence of ZB4 MoAb. Similarly, blocking by ZB4 MoAb significantly inhibited T‐cell‐mediated lysis of fresh AML cells in a CD95‐sensitive group, but not in a CD95‐refractory group. In addition CD8 + T cells expressed CD95L mRNA more abundantly than CD4 + T cells upon activation by IL‐2. These findings suggest that T‐cell‐mediated cytotoxicity against AML cells requires participation of CD95‐CD95L pathway for cytotoxic signal transduction leading to target apoptosis.