CD154 (CD40 ligand)

被引:93
作者
Schönbeck, U
Mach, F
Libby, P
机构
[1] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
CD40L/CD154; CD40; immunity; inflammation;
D O I
10.1016/S1357-2725(00)00016-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CD40 ligand, a type II transmembrane protein recently renamed CD154, was originally considered restricted to activated T lymphocytes, functioning as a mediator of T cell-dependent B cell activation, proliferation, and differentiation. However, the spectrum of CD154 expression and function has broadened considerably during recent years, establishing new roles as a central mediator of immunity and inflammation for this member of the tumor necrosis factor (TNF) gene superfamily. The emerging picture indicates that ligation of the receptor CD40 via CD154, most potently in its trimeric form, functions in two ways. CD154 modulates physiologic processes, such as T cell-mediated effector functions and general immune responses required for appropriate host defense, but also triggers the expression of pro-inflammatory mediators, such as cytokines, adhesion molecules; and matrix degrading activities, all of which are associated with the pathogenesis of chronic inflammatory diseases, e.g., autoimmune disorders, arthritis, atherosclerosis, and cancer. Accordingly, CD40/CD154 interactions have advanced as a potential therapeutic target for these diseases, whereby two opposing strategies, interruption as well as enhancement of CD40 signaling, are explored for beneficial outcomes. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:687 / 693
页数:7
相关论文
共 17 条
[1]   Detailed comparison of two molecular models of the human CD40 ligand with an x-ray structure and critical assessment of model-based mutagenesis and residue mapping studies [J].
Bajorath, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24603-24609
[2]   CD40 LIGAND AND ITS ROLE IN X-LINKED HYPER-IGM SYNDROME [J].
CALLARD, RE ;
ARMITAGE, RJ ;
FANSLOW, WC ;
SPRIGGS, MK .
IMMUNOLOGY TODAY, 1993, 14 (11) :559-564
[3]  
Clark LB, 1996, ADV IMMUNOL, V63, P43
[4]   CYCLOSPORINE-A INHIBITS CD40 LIGAND EXPRESSION IN T-LYMPHOCYTES [J].
FULEIHAN, R ;
RAMESH, N ;
HORNER, A ;
AHERN, D ;
BELSHAW, PJ ;
ALBERG, DG ;
STAMENKOVIC, I ;
HARMON, W ;
GEHA, RS .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (03) :1315-1320
[5]   HUMAN CD40-LIGAND - MOLECULAR-CLONING, CELLULAR-DISTRIBUTION AND REGULATION OF EXPRESSION BY FACTORS CONTROLLING IGE PRODUCTION [J].
GAUCHAT, JF ;
AUBRY, JP ;
MAZZEI, G ;
LIFE, P ;
JOMOTTE, T ;
ELSON, G ;
BONNEFOY, JY .
FEBS LETTERS, 1993, 315 (03) :259-266
[6]   A SOLUBLE FORM OF TRAP (CD40 LIGAND) IS RAPIDLY RELEASED AFTER T-CELL ACTIVATION [J].
GRAF, D ;
MULLER, S ;
KORTHAUER, U ;
VANKOOTEN, C ;
WEISE, C ;
KROCZEK, RA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (06) :1749-1754
[7]   The CD40-CD154 system in anti-infective host defense [J].
Grewal, IS ;
Borrow, P ;
Pamer, EG ;
Oldstone, MBA ;
Flavell, RA .
CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (04) :491-497
[8]   CD40 and CD154 in cell-mediated immunity [J].
Grewal, IS ;
Flavell, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :111-135
[9]   2 ANGSTROM CRYSTAL-STRUCTURE OF AN EXTRACELLULAR FRAGMENT OF HUMAN CD40 LIGAND [J].
KARPUSAS, M ;
HSU, YM ;
WANG, JH ;
THOMPSON, J ;
LEDERMAN, S ;
CHESS, L ;
THOMAS, D .
STRUCTURE, 1995, 3 (10) :1031-1039
[10]   Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells [J].
Kato, K ;
Cantwell, MJ ;
Sharma, S ;
Kipps, TJ .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (05) :1133-1141