2 DISTINCT PATHWAYS OF SPECIFIC KILLING REVEALED BY PERFORIN MUTANT CYTOTOXIC T-LYMPHOCYTES

被引:285
作者
KOJIMA, H
SHINOHARA, N
HANAOKA, S
SOMEYASHIROTA, Y
TAKAGAKI, Y
OHNO, H
SAITO, T
KATAYAMA, T
YAGITA, H
OKUMURA, K
SHINKAI, Y
ALT, FW
MATSUZAWA, A
YONEHARA, S
TAKAYAMA, H
机构
[1] SCI UNIV TOKYO,FAC PHARMACEUT SCI,DEPT PATHOPHYSIOL,SHINJUKU KU,TOKYO 162,JAPAN
[2] MITSUBISHI KASEI INST LIFE SCI,MOLEC IMMUNOL LAB,MACHIDA,TOKYO 194,JAPAN
[3] CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOLEC GENET,CHUO KU,CHIBA 260,JAPAN
[4] JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN
[5] CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115
[6] UNIV TOKYO,INST MED SCI,LAB ANIM RES CTR,MINATO KU,TOKYO 108,JAPAN
[7] JT INC,PHARMACEUT BASIC RES LABS,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN
关键词
D O I
10.1016/1074-7613(94)90066-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To study the contribution of putative perforin-independent mechanism in the antigen-specific target destruction by cytotoxic T lymphocytes, CD8(+) CTL lines were established from spleen cells of chimeric mice produced by injecting perforin (-/-) embryonic stem cells into blastocysts of RAG-2(-/-) mice. When tested on normal concanavalin A blasts, these perforin-deficient cytotoxic T lymphocyte lines were found to be capable of inducing antigen-specific target cell lysis accompanied by DNA degradation. In contrast, with target cells carrying a mutation in Fas molecule, perforin-independent cytotoxicity was not detectable. These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis.
引用
收藏
页码:357 / 364
页数:8
相关论文
共 44 条
[1]   CLONING AND EXPRESSION OF THE MOUSE PGK-1 GENE AND THE NUCLEOTIDE-SEQUENCE OF ITS PROMOTER [J].
ADRA, CN ;
BOER, PH ;
MCBURNEY, MW .
GENE, 1987, 60 (01) :65-74
[2]  
BEER JZ, 1983, CANCER RES, V43, P4736
[3]  
BERKE G, 1993, IMMUNOLOGY, V78, P105
[4]  
BERKE G, 1989, FUNDAMENTAL IMMUNOLO, P735
[5]   RAG-2-DEFICIENT BLASTOCYST COMPLEMENTATION - AN ASSAY OF GENE-FUNCTION IN LYMPHOCYTE DEVELOPMENT [J].
CHEN, JZ ;
LANSFORD, R ;
STEWART, V ;
YOUNG, F ;
ALT, FW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (10) :4528-4532
[6]   LPR AND GLD - SINGLE GENE MODELS OF SYSTEMIC AUTOIMMUNITY AND LYMPHOPROLIFERATIVE DISEASE [J].
COHEN, PL ;
EISENBERG, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 1991, 9 :243-269
[7]   EXTRACELLULAR ATP IN LYMPHOCYTE-T ACTIVATION - POSSIBLE ROLE IN EFFECTOR FUNCTIONS [J].
FILIPPINI, A ;
TAFFS, RE ;
SITKOVSKY, MV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (21) :8267-8271
[8]   CLONING OF AN INTERLEUKIN-4 INDUCIBLE GENE FROM CYTOTOXIC LYMPHOCYTES-T AND ITS IDENTIFICATION AS A LIPASE [J].
GRUSBY, MJ ;
NABAVI, N ;
WONG, H ;
DICK, RF ;
BLUESTONE, JA ;
SCHOTZ, MC ;
GLIMCHER, LH .
CELL, 1990, 60 (03) :451-459
[9]   FAS AND ITS LIGAND IN A GENERAL MECHANISM OF T-CELL-MEDIATED CYTOTOXICITY [J].
HANABUCHI, S ;
KOYANAGI, M ;
KAWASAKI, A ;
SHINOHARA, N ;
MATSUZAWA, A ;
NISHIMURA, Y ;
KOBAYASHI, Y ;
YONEHARA, S ;
YAGITA, H ;
OKUMURA, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (11) :4930-4934
[10]   MECHANISM OF LYMPHOCYTE-MEDIATED CYTO-TOXICITY [J].
HENKART, PA .
ANNUAL REVIEW OF IMMUNOLOGY, 1985, 3 :31-58