CD45-mediated signals can trigger shedding of lymphocyte L-selectin

The adhesion molecule L-selectin is proteolytically cleaved from thesurface of lymphocytes and neutrophils within minutes after stimulation byphorbol ester or calcium ionophores. In contrast to neutrophils, solublefactors have not been shown to induce down-regulation of L- selectin onlymphocytes. We therefore examined whether signals generated by interactionwith cell surface receptors could deliver physiological stimuli inducingthis regulatory mechanism. While cross- linking of several adhesionmolecules (CD2, CD44, alpha 4-integrin, LFA- 1) by antibody did not resultin a significant reduction of the expression of L-selectin, antibodiesagainst CD45 and Thy-1.2, both involved in the regulation of lymphocyteactivation, induced loss of cell surface L-selectin within minutes, even at4 degrees C, by shedding into the supernatant. Cross-linking of thesemolecules was shown to be essential, but Fc interactions or adherent cellswere not required. A similar response, albeit less effective, was foundafter cross-linking of CD3. Interestingly, initiation of shedding onlyoccurred in the presence of cell-cell contact, pointing to a second, as yetunknown, signal required. Loss of L-selectin induced by CD45 cross- linkingis followed by a rapid re-expression of the molecule upon incubation at 37degrees C. This reaction is also dependent on specific triggering signalsas rapid re-expression was not observed after removal of L-selectin bytrypsin. The data indicate that the protein phosphatase CD45 as well as theTCR complex itself in combination with a further, as yet unknown, cell-cellcontact-dependent stimulus have a regulatory role in the dynamic control ofL-selectin expression in lymphocytes.