Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells.
OBJECTIVE
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.
INSERM UMR S 872, Paris, France.
Emilie
E
Groyer
Antonino
A
Nicoletti
Hafid
H
Ait-Oufella
Jamila
J
Khallou-Laschet
Aditi
A
Varthaman
Anh-Thu
AT
Gaston
Olivier
O
Thaunat
Srini V
SV
Kaveri
Radek
R
Blatny
Hannes
H
Stockinger
Ziad
Z
Mallat
Giuseppina
G
Caligiuri
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005916:Globulins / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012016:Reference Values; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
D005916:Globulins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011971:Receptors, Immunologic