Interplay between TNF and Regulatory T Cells in a TNF-Driven Murine Model of Arthritis

被引：60
作者：
Biton, Jerome [1 ]
Semerano, Luca [1 ,2 ]
Delavallee, Laure [1 ]
Lemeiter, Delphine [1 ]
Laborie, Marion [3 ]
Grouard-Vogel, Geraldine [3 ]
Boissier, Marie-Christophe [1 ,2 ]
Bessis, Natacha [1 ]
机构：
[1] Univ Paris 13, EA4222, F-93000 Bobigny, France
[2] Hop Avicenne, Assistance Publ Hop Paris, Serv Rhumatol, F-93000 Bobigny, France
[3] Neovacs, F-75014 Paris, France
来源：
JOURNAL OF IMMUNOLOGY | 2011年 / 186卷 / 07期
关键词：
TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; CUTTING EDGE; ALPHA; MICE; HOMEOSTASIS; POPULATION; TOLERANCE; BLOCKADE;
D O I：
10.4049/jimmunol.1003372
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are involved in several autoimmune diseases, including rheumatoid arthritis. TNF-alpha blockers induce therapeutic benefits in rheumatoid arthritis via a variety of mechanisms. We aimed to characterize the impact on Treg of TNF-alpha overexpression in vivo and of TNF-alpha inhibiting treatments. We used human TNF-alpha transgenic mice as a model of strictly TNF-alpha-dependent arthritis. Our study showed that initial Treg frequency was lower in TNF-alpha transgenic mice than in wild-type mice. However, the course of arthritis was marked by elevation of Treg frequency and a dramatic increase in expression of TNFR2. Antagonizing TNF-alpha with either the anti-human TNF-alpha Ab (infliximab) or active immunotherapy (TNF-kinoid) increased the Treg frequency and upregulated CTLA-4, leading to enhancement of suppressor activity. Moreover, both anti-TNF-alpha strategies promoted the differentiation of a CD62L(-) Treg population. In conclusion, in an in vivo model of TNF-alpha-driven arthritis, Treg frequency increased with inflammation but failed to control the inflammatory process. Both passive and active TNF-alpha-inhibiting strategies restored the suppressor activity of Treg and induced the differentiation of a CD62L(-) Treg population. The Journal of Immunology, 2011, 186: 3899-3910.
引用
收藏
页码：3899 / 3910
页数：12
相关论文
共 37 条
[1]   Tumor necrosis factor inhibitors: Clinical implications of their different immunogenicity profiles [J].
Anderson, PJ .
SEMINARS IN ARTHRITIS AND RHEUMATISM, 2005, 34 (05) :19-22
[2]   Gene therapy of collagen-induced arthritis by electrotransfer of human tumor necrosis factor-α soluble receptor I variants [J].
Bloquel, C ;
Bessis, N ;
Boissier, MC ;
Scherman, D ;
Bigey, P .
HUMAN GENE THERAPY, 2004, 15 (02) :189-201
[3]   Shifting the imbalance from Th1/Th2 to Th17/treg: The changing rheumatoid arthritis paradigm [J].
Boissier, Marie-Christophe ;
Assier, Eric ;
Falgarone, Geraldine ;
Bessis, Natacha .
JOINT BONE SPINE, 2008, 75 (04) :373-375
[4]   Regulatory T cells (Treg) in rheumatoid arthritis [J].
Boissier, Marie-Christophe ;
Assier, Eric ;
Biton, Jerome ;
Denys, Anne ;
Falgarone, Geraldine ;
Bessis, Natacha .
JOINT BONE SPINE, 2009, 76 (01) :10-14
[5]   Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse [J].
Brunkow, ME ;
Jeffery, EW ;
Hjerrild, KA ;
Paeper, B ;
Clark, LB ;
Yasayko, SA ;
Wilkinson, JE ;
Galas, D ;
Ziegler, SF ;
Ramsdell, F .
NATURE GENETICS, 2001, 27 (01) :68-73
[6]   Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis [J].
Cao, D ;
Malmström, V ;
Baecher-Allan, C ;
Hafler, D ;
Klareskog, L ;
Trollmo, C .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (01) :215-223
[7]   CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease [J].
Cao, DJ ;
van Vollenhoven, R ;
Klareskog, L ;
Trollmo, C ;
Malmström, V .
ARTHRITIS RESEARCH & THERAPY, 2004, 6 (04) :R335-R346
[8]   Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells [J].
Chen, Xin ;
Baeumel, Monika ;
Maennel, Daniela N. ;
Howard, O. M. Zack ;
Oppenheim, Joost J. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (01) :154-161
[9]   Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood [J].
Chen, Xin ;
Subleski, Jeffrey J. ;
Hamano, Ryoko ;
Howard, O. M. Zack ;
Wiltrout, Robert H. ;
Oppenheim, Joost J. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2010, 40 (04) :1099-1106
[10]   Relationship between angiogenesis and inflammation in experimental arthritis [J].
Clavel, Gaelle ;
Valvason, Chiara ;
Yamaoka, Kunio ;
Lemeiter, Delphine ;
Laroche, Liliane ;
Boissier, Marie-Christophe ;
Bessis, Natacha .
EUROPEAN CYTOKINE NETWORK, 2006, 17 (03) :202-210
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