Role of 4-1BB in immune responses

被引:260
作者
Vinay, DS
Kwon, BS
机构
[1] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[2] Walther Oncol Ctr, Indianapolis, IN 46202 USA
[3] Walther Canc Inst, Indianapolis, IN 46202 USA
关键词
4-1BB; 4-1BBL; co-stimulation;
D O I
10.1006/smim.1998.0157
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
4-1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine-rich cell-surface molecules. Both human and mouse 4-1BB recently received HLDA nomenclature. Naive T cells lack 4-1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4-1BB, 4-1BBL is also induced and is found on activated antigen-presenting cells. Cross-linking of the 4-1BB molecule by agonistic antibody transmits a distinct anal potent co-stimulatory signal leading to the activation and differentiation of CD4(+) and CD8(+) cells. 4-1BB transmits signals through the TRAF2-NIK pathway and activates NF-kappa B. Signal relayed through 4-1BB inhibit activation-induced cell death and rescue the immune system during the post-CD28 phase. Antibodies to the 4-1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4-1BB-4-1BBL pathway may be of therapeutic use in the treatment of HN infection. 4-1BB-deficient mice show dysregulated immune responses and mount elevated Ig responses to T-dependent antigens.
引用
收藏
页码:481 / 489
页数:9
相关论文
共 45 条
[1]   FAS LIGAND MEDIATES ACTIVATION-INDUCED CELL-DEATH IN HUMAN T-LYMPHOCYTES [J].
ALDERSON, MR ;
TOUGH, TW ;
DAVISSMITH, T ;
BRADDY, S ;
FALK, B ;
SCHOOLEY, KA ;
GOODWIN, RG ;
SMITH, CA ;
RAMSDELL, F ;
LYNCH, DH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (01) :71-77
[2]   MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF HUMAN 4-1BB AND ITS LIGAND [J].
ALDERSON, MR ;
SMITH, CA ;
TOUGH, TW ;
DAVISSMITH, T ;
ARMITAGE, RJ ;
FALK, B ;
ROUX, E ;
BAKER, E ;
SUTHERLAND, GR ;
DIN, WS ;
GOODWIN, RG .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (09) :2219-2227
[3]   4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor κB [J].
Arch, RH ;
Thompson, CB .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (01) :558-565
[4]   TUMOR-NECROSIS-FACTOR RECEPTOR SUPERFAMILY MEMBERS AND THEIR LIGANDS [J].
ARMITAGE, RJ .
CURRENT OPINION IN IMMUNOLOGY, 1994, 6 (03) :407-413
[5]  
CASCINO I, 1995, J IMMUNOL, V154, P2706
[6]  
CAYABYAB M, 1994, J IMMUNOL, V152, P1523
[7]   T-CELL ACTIVATION MOLECULE 4-1BB BINDS TO EXTRACELLULAR-MATRIX PROTEINS [J].
CHALUPNY, NJ ;
PEACH, R ;
HOLLENBAUGH, D ;
LEDBETTER, JA ;
FARR, AG ;
ARUFFO, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10360-10364
[8]  
CHANG J, 1994, SCIENCE, V263, P1759
[9]  
Chu NR, 1997, J IMMUNOL, V158, P3081
[10]  
DeBenedette MA, 1997, J IMMUNOL, V158, P551