SIRPγ-CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation
Résumé
A numerous number of positive and negative signals via various molecules modulate T-cell activation. Within the various transmembrane proteins, SIRPg is of interest since it is not expressed in rodents. SIRPg interaction with CD47 is reevaluated in this study. Indeed, wshow that the anti-SIRPg mAb clone LSB2.20 previously used by others has not beenappropriately characterized. We reveal that the anti-SIRPa clone KWAR23 is a Pan antiSIRP mAb which efficiently blocks SIRPa and SIRPg interactions with CD47. We show that SIRPg expression on T cells varies with their differentiation and while being expressed on Tregs, is not implicated in their suppressive functions. SIRPg spatial reorganization atthe immune synapse is independent of its interaction with CD47. In vitro SIRPa-g/CD47 blockade with KWAR23 impairs IFN-g secretion by chronically activated T cells. In vivo in a xeno-GvHD model in NSG mice, the SIRPg/CD47 blockade with the KWAR23 significantlydelays the onset of the xeno-GvHD and deeply impairs human chimerism. In conclusion, we have shown that T-cell interaction with CD47 is of importance notably inchronic stimulation.
Domaines
Sciences du Vivant [q-bio]
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