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 activation. We have investigated the ability of five anti-CD44 monoclonal antibodies (MoAb) including 15C6, 18A3, BU75 (Ancell), J173 (Immunotech), and L178 (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 cells 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 binding of MoAb directly to T cells without the involvement of monocytes or Fc receptors. In addition, the inhibitory anti-CD44 MoAb clearly suppressed intracellular 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 hyaluronan (HA) to CD44 molecules. These results suggest that anti-CD44 MoAb directed to HA-binding site could selectively inhibit CD3-mediated T cell activation. Furthermore, CD44-mediated inhibitory signals would be linked to the blocking of early CD3-mediated signal transduction.
Sugiyama
K
K
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Komada
Y
Y
Deguchi
T
T
Zhang
X L
XL
Azuma
E
E
Ido
M
M
Yamamoto
H
H
Sakurai
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D002118:Calcium