BYSTANDER APOPTOSIS INDUCED BY CD8+ CYTOTOXIC T-CELL (CTL) CLONES - IMPLICATIONS FOR CTL LYTIC MECHANISMS

被引:29
作者
BURROWS, SR [1 ]
FERNAN, A [1 ]
ARGAET, V [1 ]
SUHRBIER, A [1 ]
机构
[1] QUEENSLAND INST MED RES, BANCROFT CTR, 300 HERSTON RD, BRISBANE, QLD 4029, AUSTRALIA
基金
英国惠康基金;
关键词
LETHAL HIT; PERFORIN; T-LYMPHOCYTE; UNIDIRECTIONAL LYSIS;
D O I
10.1093/intimm/5.9.1049
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytotoxic T lymphocyte (CTL) mediated killing has classically been associated with a high level of specificity for the target cell. However, when CTL clones and specific target cells were copelleted with innocent bystander cells for which the CTL was not specific, these bystander cells were also lysed. Bystander lysis did not depend on HLA compatibility between effector and bystander cell. Indeed bystander lysis was particularly efficient during cognate synthetic peptide induced CTL - CTL killing. Bystander lysis was species unrestricted. Lytic activity could not be transferred in supernatants nor could it be inhibited by anti-tumor necrosis factor antibodies. Perforin sensitive red blood cells were very inefficiently bystander lysed. Bystander cell death was characterized by DNA fragmentation indicative of apoptosis or programmed cell death. Bystander lysis thus appeared to be due to the apoptotic CTL lytic mediator(s). Importantly, CTL were not resistant to bystander lysis induced by other CTL; nor did they become resistant when they were actively killing target cells. Since it is well established that CTL survive the delivery of their own lytic mediators, these results suggest that CTL induced apoptosis is a membrane mediated event.
引用
收藏
页码:1049 / 1058
页数:10
相关论文
共 47 条
  • [1] INVITRO SELECTION OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS ESCAPE MUTANTS BY CYTOTOXIC LYMPHOCYTES-T
    AEBISCHER, T
    MOSKOPHIDIS, D
    ROHRER, UH
    ZINKERNAGEL, RM
    HENGARTNER, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (24) : 11047 - 11051
  • [2] SEQUENCE VARIATION OF CYTOTOXIC T-CELL EPITOPES IN DIFFERENT ISOLATES OF EPSTEIN-BARR-VIRUS
    APOLLONI, A
    MOSS, D
    STUMM, R
    BURROWS, S
    SUHRBIER, A
    MISKO, I
    SCHMIDT, C
    SCULLEY, T
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (01) : 183 - 189
  • [3] BARKER E, 1989, CANCER RES, V49, P5007
  • [4] LYMPHOCYTE-TRIGGERED INTERNAL TARGET DISINTEGRATION
    BERKE, G
    [J]. IMMUNOLOGY TODAY, 1991, 12 (11): : 396 - 399
  • [5] THE SPECIFICITY OF RECOGNITION OF A CYTOTOXIC LYMPHOCYTE-T EPITOPE
    BURROWS, SR
    RODDA, SJ
    SUHRBIER, A
    GEYSEN, HM
    MOSS, DJ
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (01) : 191 - 195
  • [6] BURROWS SR, 1992, IMMUNOLOGY, V76, P174
  • [7] EXTRACELLULAR ATP AS A POSSIBLE MEDIATOR OF CELL-MEDIATED CYTOTOXICITY
    DIVIRGILIO, F
    PIZZO, P
    ZANOVELLO, P
    BRONTE, V
    COLLAVO, D
    [J]. IMMUNOLOGY TODAY, 1990, 11 (08): : 274 - 277
  • [8] PURIFIED PERFORIN INDUCES TARGET-CELL LYSIS BUT NOT DNA FRAGMENTATION
    DUKE, RC
    PERSECHINI, PM
    CHANG, S
    LIU, CC
    COHEN, JJ
    YOUNG, JDE
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 170 (04) : 1451 - 1456
  • [10] T-CELL RECEPTOR CROSS-LINKING TRANSIENTLY STIMULATES ADHESIVENESS THROUGH LFA-1
    DUSTIN, ML
    SPRINGER, TA
    [J]. NATURE, 1989, 341 (6243) : 619 - 624