INTERACTION BETWEEN ENDOTHELIUM AND CD4+CD45RA+ LYMPHOCYTES ROLE OF THE HUMAN CD38 MOLECULE

CD38 is a type II transmembrane glycoprotein, which is widely used as a marker for immature and activated lymphocytes, as well as plasma cel ls. Although its functional role and natural ligand are not known, CD3 8 has been shown to transduce activation signals to lymphocytes. Our w ork shows that CD38 is preferentially expressed by CD4(+)CD45RA(+) cel ls, but not by CD4(+)CD45R0(+) cells. CD4(+)CD45RA(+) cells are report ed to respond poorly to stimuli acting through the CD3/TCR in vitro an d to display unique migration pathways in vivo. Cross-linking of CD38 by mAb did not overcome the hyporesponsiveness of CD4(+) resting/naive cells to several activation stimuli; in contrast, CD38 engagement by mAb specifically inhibited their binding with human vein endothelial c ells. These data suggest that CD38 may play a role in lymphocyte migra tion. The same inhibitory effect was detected on the (human x mouse) h ybrid cell line CP410.A10, which expresses human CD38, but not on its CD38(-) subclone CP14. CD38 mAb did not inhibit the conventional bindi ng assay between endothelium and several human CD38(+) T and B cell li nes. However, the inhibition was apparent when the binding assay was p erformed at 4 degrees C on a rocking shelf, conditions that minimized integrin function. These data suggest that CD38 mediates weak cell bin ding to endothelium, which is effective even in dynamic conditions. Th ese features are reminiscent of those exerted by selectins, which are adhesion molecules that account for leukocyte rolling on vascular endo thelial cells and play an important role in lymphocyte homing.