DYSREGULATED FAS AND BCL-2 EXPRESSION LEADING TO ENHANCED APOPTOSIS IN T-CELLS OF MULTIPLE-MYELOMA PATIENTS

被引:55
作者
MASSAIA, M [1 ]
BORRIONE, P [1 ]
ATTISANO, C [1 ]
BARRAL, P [1 ]
BEGGIATO, E [1 ]
MONTACCHINI, L [1 ]
BIANCHI, A [1 ]
BOCCADORO, M [1 ]
PILERI, A [1 ]
机构
[1] UNIV TURIN,OSPED MOLINETTE,DIPARTIMENTO MED & ONCOL SPERIMENTALE,DIV EMATOL,TURIN,ITALY
关键词
D O I
10.1182/blood.V85.12.3679.bloodjournal85123679
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest pas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo. (C) 1995 by The American Society of Hematology.
引用
收藏
页码:3679 / 3687
页数:9
相关论文
共 41 条
[1]   THE SIGNIFICANCE OF LOW BCL-2 EXPRESSION BY CD45RO-T-CELLS IN NORMAL INDIVIDUALS AND PATIENTS WITH ACUTE VIRAL-INFECTIONS - THE ROLE OF APOPTOSIS IN T-CELL MEMORY [J].
AKBAR, AN ;
BORTHWICK, N ;
SALMON, M ;
GOMBERT, W ;
BOFILL, M ;
SHAMSADEEN, N ;
PILLING, D ;
PETT, S ;
GRUNDY, JE ;
JANOSSY, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (02) :427-438
[2]   FAS TRANSDUCES ACTIVATION SIGNALS IN NORMAL HUMAN T-LYMPHOCYTES [J].
ALDERSON, MR ;
ARMITAGE, RJ ;
MARASKOVSKY, E ;
TOUGH, TW ;
ROUX, E ;
SCHOOLEY, K ;
RAMSDELL, F ;
LYNCH, DH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) :2231-2235
[3]  
CARBONARI M, 1994, BLOOD, V83, P1268
[4]  
CIMINO G, 1990, BRIT J HAEMATOL, V57, P373
[5]   THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS [J].
CLARKE, AR ;
PURDIE, CA ;
HARRISON, DJ ;
MORRIS, RG ;
BIRD, CC ;
HOOPER, ML ;
WYLLIE, AH .
NATURE, 1993, 362 (6423) :849-852
[6]  
COHEN JJ, 1993, IMMUNOL TODAY, V14, P126, DOI 10.1016/0167-5699(93)90214-6
[7]  
DIANZANI U, 1988, BLOOD, V72, P1064
[8]  
DURIE BGM, 1977, RECENT ADV HAEMATOLO, P243
[9]   ACTIVATION-INDUCED DEATH BY APOPTOSIS IN CD4+ T-CELLS FROM HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED ASYMPTOMATIC INDIVIDUALS [J].
GROUX, H ;
TORPIER, G ;
MONTE, D ;
MOUTON, Y ;
CAPRON, A ;
AMEISEN, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (02) :331-340
[10]  
HUANG L, 1993, J IMMUNOL, V151, P1844