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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

陈同辛YOSHIHIRO KOMADA YAN-WEN ZHou XAO-LI ZHANG TONG-XIN CHEN SHIGEKI TANAKA EIIcHI AzuMA

British Journal of Haematology, 1997, 96, 147-157,-0001,():

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摘要/描述

Sulnlnarg. AD0ptotic cell death is induced by the cross-linking of Fas/APO-1 receptor fCD951 in acute myefogenous leukaemia fAMLl cells Since CD95 ligand fCD95L1 isexpressed on interleukin-2 fIL-21-activated T cells we Investigated the involvenlent of CD95-CD95L pathway in T cell-mediated cytotoxicitv against AML cells Activated CD8+ T cells could efficlently kfll a parental CD95-sensitlye 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 monocfonal antibodv (MoAb) against CD95. ZB4. caused a significant inhibition of T-cell-mediated cvtotoxicitv against M1VEL-1 cells but not against MML-1R cells hlteresttngly, MML-1 cells underwent the classic nuclear morphologic changes and DNA fragmentation characteristic of apoptOSiS when culturedwith activatedTcells Enmneratinn ofapoptoticand 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 flesh AML cells in a CD95-sensitive group, but not in a CD95-refractory group In addition CD8+ T cells expressed CD95L 111RNA more abundantly than CD4+ T cells upon activation bv 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.

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