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*
Allergy Research Laboratory, Research Center of CHUM, Notre-Dame Hospital, University of Montreal, and
Department of Obstetrics and Gynecology, University of Montreal, Quebec, Canada
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-
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- in primary
cultures, which was correlated with a decrease of the IL-12Rß2 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.
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