Leukocyte CD47 plays a critical role in T‐cell recruitment in vivo through affinity regulation of LFA‐1 and VLA‐4 integrins

Abstract

Host defense critically depends on effector T‐cell adhesive interaction with the vascular endothelium. CD47 is broadly expressed and participates in leukocyte recruitment and immune functions. CD47 (Integrin Associated Protein) functionally associates with multiple integrins. Here we examined the hypothesis that CD47 regulates LFA‐1 and VLA‐4 adhesive function in T‐cell recruitment. Intravital microscopy studies revealed that transferred CD47ko Th1 cells have reduced adhesion to WT TNFα‐inflamed cremaster microvessels versus WT Th1 cells. Studies in an in vitro flow model showed that CD47ko Th1 cells, as compared to WT cells, also have reduced adhesion and diapedesis of TNFα‐activated endothelium, and bind less to immobilized ICAM‐1 and VCAM‐1. Similarly, human Jurkat T‐cells lacking CD47 bind less to TNFα‐activated endothelium and to immobilized ICAM‐1 and VCAM‐1. Finally, Jurkat CD47 null cells have a reduction in Mn+2‐induced binding of mAb 24 (67%↓) and KIM127 (51%↓), which detect activated conformations of β2 integrins. However, the absence of CD47 does not affect their β2 integrin dependent “adhesion strengthening” to ICAM‐1 as determined by a cell detachment assay. Taken together, our results indicate CD47 primarily affects T‐cell VLA‐4 and LFA‐1 affinity regulation, and this function is necessary for T‐cell adhesion and diapedesis. Supported by NIH HL‐36028 and AHA fellowship 11POST7730055.