CD45-MEDIATED SIGNALS CAN TRIGGER SHEDDING OF LYMPHOCYTE L-SELECTIN

The adhesion molecule L-selectin is proteolytically cleaved from the s urface of lymphocytes and neutrophils within minutes after stimulation by phorbol ester or calcium ionophores, In contrast to neutrophils, s oluble factors have not been shown to induce down-regulation of L-sele ctin on lymphocytes. We therefore examined whether signals generated b y interaction with cell surface receptors could deliver physiological stimuli inducing this regulatory mechanism. While crosslinking of seve ral adhesion molecules (CD2, CD44, alpha(4)-integrin, LFA-1) by antibo dy did not result in a significant reduction of the expression of L-se lectin, antibodies against CD45 and Thy-1.2, both involved in the regu lation of lymphocyte activation, induced loss of cell surface L-select in within minutes, even at 4 degrees C, by shedding into the supernata nt. Cross-linking of these molecules was shown to be essential, but Fc interactions or adherent cells were not required. A similar response, albeit less effective, was found after cross-linking of CD3, Interest ingly, initiation of shedding only occurred in the presence of cell-ce ll contact, pointing to a second, as yet unknown, signal required. Los s of L-selectin induced by CD45 cross-linking is followed by a rapid r e-expression of the molecule upon incubation at 37 degrees C. This rea ction is also dependent on specific triggering signals as rapid re-exp ression was not observed after removal of L-selectin by trypsin, The d ata indicate that the protein phosphatase CD45 as well as the TCR comp lex itself in combination with a further, as yet unknown, cell-cell co ntact-dependent stimulus have a regulatory role in the dynamic control of L-selectin expression in lymphocytes.