New insights into the pathogenesis of rheumatoid arthritis

被引:91
作者
Weyand, CM [1 ]
机构
[1] Mayo Clin & Mayo Fdn, Dept Med, Div Rheumatol, Rochester, MN 55905 USA
关键词
rheumatoid arthritis; pathogenesis; T cells; animal models; T-cell clonal expansion; T-cell homeostasis;
D O I
10.1093/oxfordjournals.rheumatology.a031491
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
T lymphocytes play a critical role in the inflammatory process of rheumatoid arthritis (RA). Studies in a new animal model of RA, created by implanting human inflamed synovium into SCID mice, have confirmed that the production of matrix-degrading enzymes and pro-inflammatory cytokines is ultimately under T-cell control. T-cell dysfunction in RA patients also alters T-cell dynamics, resulting in profound abnormalities in T-cell pool composition. The cause and consequences of altered T-cell dynamics in RA are not yet understood, but factors determining T-cell homeostasis include the generation of new T cells, loss of T cells during immune responses and self-renewal of T cells within the system. Understanding the mechanisms that govern the formation of the T-cell pool in RA emphasizes the dynamic and quantitative aspects of lymphocyte behaviour in RA and has profound therapeutic implications when devising strategies to counteract T-cell dysfunction.
引用
收藏
页码:3 / 8
页数:6
相关论文
共 27 条
[1]  
Goronzy J J, 1998, Int Rev Immunol, V17, P339, DOI 10.3109/08830189809054410
[2]   THE SHARED EPITOPE HYPOTHESIS - AN APPROACH TO UNDERSTANDING THE MOLECULAR-GENETICS OF SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS [J].
GREGERSEN, PK ;
SILVER, J ;
WINCHESTER, RJ .
ARTHRITIS AND RHEUMATISM, 1987, 30 (11) :1205-1213
[3]  
Iannone F, 1996, BRIT J RHEUMATOL, V35, P397
[4]   EMERGENCE OF OLIGOCLONAL T-CELL POPULATIONS FOLLOWING THERAPEUTIC T-CELL DEPLETION IN RHEUMATOID-ARTHRITIS [J].
JENDRO, MC ;
GANTEN, T ;
MATTESON, EL ;
WEYAND, CM ;
GORONZY, JJ .
ARTHRITIS AND RHEUMATISM, 1995, 38 (09) :1242-1251
[5]   Production of cytokines and metalloproteinases in rheumatoid synovitis is T cell dependent [J].
Klimiuk, PA ;
Yang, HY ;
Goronzy, JJ ;
Weyand, CM .
CLINICAL IMMUNOLOGY, 1999, 90 (01) :65-78
[6]   Perturbation of the T-cell repertoire in patients with unstable angina [J].
Liuzzo, G ;
Kopecky, SL ;
Frye, RL ;
O'Fallon, WM ;
Maseri, A ;
Goronzy, JJ ;
Weyand, CM .
CIRCULATION, 1999, 100 (21) :2135-2139
[7]   Functional CD40 ligand is expressed by T cells in rheumatoid arthritis [J].
MacDonald, KPA ;
Nishioka, Y ;
Lipsky, PE ;
Thomas, R .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (09) :2404-2414
[8]   Expansion of unusual CD4+ T cells in severe rheumatoid arthritis [J].
Martens, PB ;
Goronzy, JJ ;
Schaid, D ;
Weyand, CM .
ARTHRITIS AND RHEUMATISM, 1997, 40 (06) :1106-1114
[9]  
Namekawa T, 1998, ARTHRITIS RHEUM, V41, P2108
[10]   Multiple mechanisms support oligoclonal T cell expansion in rheumatoid synovitis [J].
Rittner, HL ;
Zettl, A ;
Jendro, MC ;
BartzBazzanella, P ;
Goronzy, JJ ;
Weyand, CM .
MOLECULAR MEDICINE, 1997, 3 (07) :452-465