CD3-mediated T-cell activation is inhibited by anti-CD44 monoclonal antibodies directed to the hyaluronan-binding region

The CD44 molecule has been shown to play a role in T cell adhesion and acti vation. We have investigated the ability of five anti-CD44 monoclonal antib odies (MoAb) including 15C6, 18A3, BU75 (Ancell), J173 (Immunotech), and L1 78 (Becton Dickinson) to regulate T cell activation. Three MoAb: 15C6, BU75 , and J173 were found to selectively inhibit DNA synthesis, interleukin-2 ( IL-2) receptor expression, and G1-->S transition of the cell cycle in T cel ls stimulated with anti-CD3 MoAb. None of anti-CD44 MoAb had influence on T cell proliferation induced by IL-2 or phorbol 12-myristate 13-acetate plus ionomycin, Inhibition of the CD3 pathway by anti-CD44 MoAb occurred by bin ding of MoAb directly to T cells without the involvement of monocytes or Fe receptors. In addition, the inhibitory anti-CD44 MoAb clearly suppressed i ntracellular calcium mobilization in T cells stimulated with anti-CD3 MoAb. Interestingly, the ability of anti-CD44 MoAb to inhibit T cell activation was well correlated with their capability to block the binding of hyalurona n (HA) to CD44 molecules. These results suggest that anti-CD44 MoAb directe d to HA-binding site could selectively inhibit CD3-mediated T cell activati on. Furthermore, CD44-mediated inhibitory signals would be linked to the bl ocking of early CD3-mediated signal transduction.