Cross-Linking of Protein S Bound to Lymphocytes Promotes Aggregation and Inhibits Proliferation

Recently, we reported that expression of the anticoagulant protein S is IL-4-inducible in primary T cells, and that protein S inhibits lymphoid cell procoagulant activity. Here, using a flow cytometric assay, we demonstrate that protein S binds to the surface of B and T lymphocytes. In addition, we show that cross-linking of protein S bound to lymphocytes induces aggregation and inhibits growth in cultures of primary B and T lymphocytes. Thus, our studies suggest that protein S is an IL-4-inducible T cell product that can affect B and T cell growth and aggregation via a lymphocyte protein S receptor. Interestingly, protein S joins thrombin and factor Xa as coagulation factors that modulate lymphocyte activation, suggesting that the clotting pathway may regulate wound-related inflammatory responses.