Rescuing CD4+CD25+ regulatory T-cell functions in rheumatoid arthritis by cytokine-targeted monoclonal antibody therapy

被引：57

作者：

Bayry, Jagadeesh

Siberil, Sophie

Triebel, Frederic

Tough, David F.

Kaveri, Srin V.

机构：

[1] Univ Paris 06, INSERM UMR S 872, Univ Paris 05,Ctr Rech Cordeliers, Equipe Immunopathol & Therapeut Immunointervent 1, F-75006 Paris, France

[2] Univ Paris Sud, Fac Pharm, Immutep SA, F-92296 Chatenay Malabry, France

[3] GlaxoSmithKline, RI CEDD, Target Discovery, Stevenage SG1 2NY, Herts, England

来源：

DRUG DISCOVERY TODAY | 2007年 / 12卷 / 13-14期

关键词：

D O I：

10.1016/j.drudis.2007.05.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

CD4+CD25+ regulatory T cells (Tregs) play a crucial role in controlling the development of autoimmune diseases such as rheumatoid arthritis (RA). However, despite an increased number of Tregs, the persistence of inflammation in the rheumatoid joints suggests that Tregs are unable to suppress ongoing disease, perhaps due to an inhibition of their functions by pro-inflammatory cytokines. Treatment of RA patients with anti-TNF-alpha monoclonal antibodies such as infliximab and adalimumab has been found to induce and restore the functions of Tregs. Thus, manipulation of the pro-inflammatory environment in the inflamed synovia via neutralization of inflammatory cytokines by monoclonal antibodies could represent a novel therapeutic strategy for restoring the suppressive functions of Tregs and induction and/or expansion of Tregs in order to reinforce tolerance mechanisms.

引用

页码：548 / 552

页数：5

共 62 条

[21] IL-32, a proinflammatory cytokine in rheumatoid arthritis [J].

Joosten, LAB ;

Netea, MG ;

Kim, SH ;

Yoon, DY ;

Oppers-Walgreen, B ;

Radstake, TRD ;

Barrera, P ;

van de Loo, FAJ ;

Dinarello, CA ;

van den Berg, WB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (09) :3298-3303

[22] Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis:: an important factor in pathogenesis, counter-regulated by endogenous IFN-γ [J].

Kelchtermans, H ;

De Klerck, B ;

Mitera, T ;

Van Balen, M ;

Bullens, D ;

Billiau, A ;

Leclercq, G ;

Matthys, P .

ARTHRITIS RESEARCH & THERAPY, 2005, 7 (02) :R402-R415

[23] An essential role for Scurfin in CD4+CD25+ T regulatory cells [J].

Khattri, R ;

Cox, T ;

Yasayko, SA ;

Ramsdell, F .

NATURE IMMUNOLOGY, 2003, 4 (04) :337-342

[24]

LANCHBURY JS, 1992, CLIN EXP RHEUMATOL, V10, P301

[25] Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood [J].

Lawson, C. A. ;

Brown, A. K. ;

Bejarano, V. ;

Douglas, S. H. ;

Burgoyne, C. H. ;

Greenstein, A. S. ;

Boylston, A. W. ;

Emery, P. ;

Ponchel, F. ;

Isaacs, J. D. .

RHEUMATOLOGY, 2006, 45 (10) :1210-1217

[26] Regulatory T cells in rheumatoid arthritis [J].

Leipe, J ;

Skapenko, A ;

Lipsky, PE ;

Schulze-Koops, H .

ARTHRITIS RESEARCH & THERAPY, 2005, 7 (03) :93-99

[27] T-regulatory 1 cells:: A novel subset of CD4+T cells with immunoregulatory properties [J].

Levings, MK ;

Roncarolo, MG .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 106 (01) :S109-S112

[28] Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis [J].

Li, J. ;

Shen, W. ;

Kong, K. ;

Liu, Z. .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2006, 64 (05) :515-522

[29] Infliximab and methotrexate in the treatment of rheumatoid arthritis [J].

Lipsky, PE ;

van der Heijde, DMFM ;

St Clair, EW ;

Furst, DE ;

Breedveld, FC ;

Kalden, JR ;

Smolen, JS ;

Weisman, M ;

Emery, P ;

Feldmann, M ;

Harriman, GR ;

Maini, RN .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (22) :1594-1602

[30] The genetic and immunopathological processes underlying collagen-induced arthritis [J].

Luross, JA ;

Williams, NA .

IMMUNOLOGY, 2001, 103 (04) :407-416

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