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

被引：59

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

页码：3899 / 3910

页数：12

共 37 条

[21] CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis [J].