Molecular mechanisms underlying lymphocyte recirculation. II. Differential regulation of LFA-1 in the interaction...

Although it has been suggested that LFA-1 is one of the important molecules mediating interaction between lymphocytes and high endothelial (HE) cells, the implication was based on the observation that lymphocyte binding to high endothelial venules in frozen lymph node sections was partially inhibited by anti-LFA-1 monoclonal antibody at 4 degrees C. However, it has previously been unequivocally demonstrated that LFA-1 molecule is unable to function at this low temperature. To assess the actual involvement of LFA-1 in lymphocyte-HE cell interaction at body temperature, we examined effects of newly developed anti-rat LFA-1 and anti-rat ICAM-1 monoclonal antibody on binding of resting or activated lymphocytes to a rat HE cell line at 37 degrees C. We found that (a) LFA-1/ICAM-1-independent pathway was predominant in the interaction between resting lymphocytes and HE cells, indicating that LFA-1 functions little, if any, in the interaction and (b) lymphocyte triggering through CD3 significantly increased binding inducing a LFA-1/ICAM-1-dependent pathway, whereas phorbol 12-myristate 13-acetate stimulation also enhanced lymphocyte binding but inducing a LFA-1-dependent/ICAM-1-independent pathway. In both cases no apparent alteration in LFA-1 expression was observed, suggesting that the increase in lymphocyte adhesion was not due to quantitative but a qualitative change induced in LFA-1 molecule upon lymphocyte stimulation. These findings suggest that LFA-1 is normally inert but can be "switched" upon lymphocyte stimulation to participate in lymphocyte-HE cell interaction, and that the LFA-1's ligand specificity can be differentially regulated at the lymphocyte-HE venule interface.