1. Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells.
- Author
-
Groyer E, Nicoletti A, Ait-Oufella H, Khallou-Laschet J, Varthaman A, Gaston AT, Thaunat O, Kaveri SV, Blatny R, Stockinger H, Mallat Z, and Caligiuri G
- Subjects
- Animals, Atherosclerosis pathology, Disease Models, Animal, Gene Transfer Techniques, Lymphocyte Activation, Mice, Mice, Knockout, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Receptors, Immunologic metabolism, Reference Values, Treatment Outcome, Atherosclerosis drug therapy, Atherosclerosis immunology, Globulins therapeutic use, Platelet Endothelial Cell Adhesion Molecule-1 immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Objectives: This study was designed to evaluate whether replacing CD31 (PECAM-1) signaling can restore the regulation of lymphocyte activation and improve experimental atherosclerosis., Background: Atherosclerosis, the principal cause of myocardial infarction and stroke, is due to the development of a pathogenic immune response within the vascular wall and is aggravated by the reduction of regulatory T-cells. CD31, a transmembrane adhesion molecule with inhibitory signaling functions, is physiologically expressed on blood and vascular resting cells but is lost in pathologic conditions associated with atherosclerosis., Methods: Replacement therapy with a CD31 receptor globulin (Rg) was delivered by in vivo gene transfer in 6-week-old apolipoprotein E knockout mice (n = 14 per group) every 5 weeks for 6 months. Control groups were treated with a truncated CD31Rg or with vehicle alone. At the end of the study, plaque size and morphology and blood T-cell compartment were analyzed in all mice., Results: Atherosclerotic lesions of CD31Rg-treated mice were smaller (p < 0.01) and showed less neovascularization and intraplaque hemorrhage (p < 0.05) compared with control subjects. Furthermore, circulating regulatory T-cells were increased in vivo (p < 0.01) and showed normal suppressive function on proliferation of conventional T-cells in vitro. Indeed, CD31Rg treatment led to blunted blood T-cell activation (p < 0.05) and reduced T-cell infiltration within plaques (p < 0.01)., Conclusions: Our data suggest that CD31 plays a key role in the regulation of the immune response linked to atherosclerosis. CD31-targeting therapeutic approaches may therefore be envisaged for preventing and treating atherosclerotic diseases.
- Published
- 2007
- Full Text
- View/download PDF