Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis

被引:30
作者
Charbonnier, Louis-Marie [1 ,2 ]
Han, Wanda G. H. [3 ]
Quentin, Julie [1 ,2 ]
Huizinga, Tom W. J. [3 ]
Zwerina, Jochen [4 ]
Toes, Rene E. M. [3 ]
Jorgensen, Christian [1 ,2 ,5 ]
Louis-Plence, Pascale [1 ,2 ]
机构
[1] CHU St Eloi, INSERM, U844, F-34295 Montpellier 05, France
[2] Univ Montpellier 1, F-34000 Montpellier, France
[3] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2300 RA Leiden, Netherlands
[4] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany
[5] CHU Lapeyronnie, F-34000 Montpellier, France
关键词
Arthritis; Regulatory T cells; IL-10; Dendritic cells; Immunomodulation; Autoimmunity; COLLAGEN-INDUCED ARTHRITIS; NONOBESE DIABETIC MICE; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMATURE DENDRITIC CELLS; TNF-ALPHA THERAPY; IN-VIVO; CUTTING EDGE; NKT CELLS; TGF-BETA;
D O I
10.1016/j.jaut.2009.10.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have previously demonstrated, in the collagen-induced arthritis model (CIA), that repetitive injections of immature bone-marrow-derived dendritic cells (iDCs) induce the expansion of a population of CD4CD49b-expressing cells, and that their adoptive transfer results in protection against CIA in a prophylactic setting. However, the in vivo mechanism responsible for their expansion, as well as their therapeutic potential in established disease remains to be defined. In the present study, we show that expression of the MHC class II molecules on iDCs is required for their expansion thus identifying these cells as MHC class II-restricted T cells. Using adoptive transfer of Thy1.1 positive cells, it is shown that iDC-induced CD4(+)CD49b(+) T cells home to the lymph nodes draining the inflamed tissue. The high immunomodulatory potential of these cells was underscored following their adoptive transfer in a model of contact hypersensitivity. Finally, we assessed and compared the therapeutic potential of iDC-inducible CD4(+)CD49b(+) T cells with that of iDCs in established CIA. Repetitive injections of iDCs in arthritic mice failed to decrease the severity of established disease. In contrast however, a single injection of iDC-induced CD4(+)CD49b(+) T cells reversed clinical symptoms of arthritis and provided long-lasting protection. Together, our data indicate that iDC-induced CD4(+)CD49b(+) T cells are bona fide T regulatory cells with strong immunomodulatory properties that are not only able to prevent disease onset, but also to interfere with an ongoing inflammatory immune response. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:390 / 399
页数:10
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