Thrombospondin/CD47 interaction:: A pathway to generate regulatory T cells from human CD4+CD25- T cells in response to inflammation

被引:132
作者
Grimbert, Philippe
Bouguermouh, Salim
Baba, Nobuyasu
Nakajima, Toshiharu
Allakhverdi, Zoulfia
Braun, Deborah
Saito, Hirohisa
Rubio, Manuel
Delespesse, Guy
Sarfati, Marika
机构
[1] Ctr Hosp Univ Montreal, Immunoregulat Lab, Hop Notre Dame, Res Ctr, Montreal, PQ H2L 4M1, Canada
[2] Ctr Hosp Univ Montreal, Allergy Lab, Hop Notre Dame, Res Ctr, Montreal, PQ H2L 4M1, Canada
[3] Res Ctr Allergy & Immunol, Inst Phys & Chem Res, Lab Allergy Transcriptome, Tokyo, Japan
[4] Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Tokyo, Japan
关键词
D O I
10.4049/jimmunol.177.6.3534
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Thymus-derived CD4(+) CD25(+) T regulatory cells (Tregs) are essential for the maintenance of self-tolerance. What critical factors and conditions are required for the extra-thymic development of Tregs remains an important question. In this study, we show that the anti-inflammatory extracellular matrix protein, thrombospondin-1, promoted the generation of human peripheral regulatory T cells through the ligation of one of its receptor, CD47. CD47 stimulation by mAb or a thrombospondin-1 peptide induced naive or memory CD4(+)CD25(-) T cells to become suppressive. The latter expressed increased amounts of CTLA-4, OX40, GITR, and Foxp3 and inhibited autologous Th0, Th1, and Th2 cells. Their regulatory activity was contact dependent, TGF-beta independent, and partially circumvented by IL-2. This previously unknown mechanism to induce human peripheral Tregs in response to inflammation may participate to the limitation of collateral damage induced by exacerbated responses to self or foreign Ags and thus be relevant for therapeutic intervention in autoimmune diseases and transplantation.
引用
收藏
页码:3534 / 3541
页数:8
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