IL-16 INHIBITION OF CD3-DEPENDENT LYMPHOCYTE-ACTIVATION AND PROLIFERATION

We have recently described the cDNA and predicted protein structure of a natural soluble CD4 ligand, IL-16, IL-16 is chemotactic for CD4(+) T cells and induces functional IL-2 receptors in CD4(+) T cells. The b inding of IL-16 to CD4 results in activation of p56(lck), whose adapto r function is essential for the chemotactic response, Subsequently, in creases in intracellular Ca2+ and phosphatidylinositol 1,4,5-trisphosp hate occur, as does translocation of protein kinase C from cytosol to membrane. Because of the similarities between these signals and functi ons and those noted for the CD4 ligand HIV-1 gp120, we investigated th e potential regulatory effects of IL-16 on CD3/TCR-mediated lymphocyte activation, Preincubation of human T cells with IL-16 up to 24 h befo re activation with plate-bound anti-CD3 Abs reduced T cell activation by 80%, as monitored by IL-2R expression and [H-3]thymidine uptake. If IL-16 was added following anti-CDS activation, no suppression was not ed, The suppressive effects of preincubation with IL-16 were not rescu ed by the addition of rIL-2 and were not the result of priming for ant i-CD3-induced apoptosis, In addition, IL-16 had no effect on surface e xpression of CD3 or CD4. However, IL-16 did reduce the magnitude of th e anti-CD3-induced intracellular Ca2+ increase, These studies indicate that while the interaction of CD4 with its natural ligand, IL-16, res ults in Ag-independent chemotaxis and IL-2R expression, this pro-infla mmatory state is associated with subsequent transient inhibition of re sponsiveness via the CD3/TCR complex.