CD47 ligation selectively inhibits the development of human naive T cells into Th1 effectors.
The CD47 Ag, also named integrin-associated protein, was recently reported to regulate the production of IL-12 by human monocytes and dendritic cells. The present study shows that CD47 ligation by CD47 mAb in primary cultures of cord blood mononuclear cells inhibits IL-12-driven Th1 cell development, as revealed by the cytokine secretion profile at restimulation and IFN-gamma production at the single-cell level. F(ab')(2) fragments of CD47 mAb or the synthetic peptide 4N1K, corresponding to the CD47 binding site of thrombospondin, display the same activity. CD47 engagement does not change the phenotype of IL-12-primed cells from Th1 to Th2 or affect IL-4-induced Th2 cell development. Moreover, CD47 mAb inhibits IL-12- but not IL-4-induced IL-2 production as well as IFN-gamma in primary cultures, which was correlated with a decrease of the IL-12Rbeta2 chain expression. Inclusion of exogenous IL-2 at priming corrects IL-12R expression as well as the inhibition of Th1 cell development. The data thus underline the role of IL-2 in Th1 cell development and further suggest that targeting IL-2 and IL-12 simultaneously may have some therapeutic advantage in Th1 autoimmune diseases.
Avice
M N
MN
Allergy Research Laboratory, Research Center of CHUM, Notre-Dame Hospital, University of Montreal, and Department of Obstetrics and Gynecology, University of Montreal, Quebec, Canada.
Rubio
M
M
Sergerie
M
M
Delespesse
G
G
Sarfati
M
M
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D008024:Ligands; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D006131:Growth Inhibitors; D008024:Ligands; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12