Tenascin suppresses CD3-mediated T cell activation.

Tenascin (TN) is an extracellular matrix protein which interferes with fibronectin (FN)-dependent cell attachment and activation as a natural antagonist to FN action. In this study, we examined the inhibitory effect of TN on T cell proliferation induced by immobilized anti-CD3 Ab combined with various costimulators in a serum-free condition. Consistent with previous studies, human T cell activation induced by anti-CD3 plus FN was completely inhibited by the addition of TN. Interestingly, TN could interfere with T cell proliferations costimulated by various very late activation antigen (VLA) integrin/ligand interactions such as VLA-4/FN, VLA-5/FN and VLA-6/laminin. Furthermore, lymphocyte function-associated antigen 1 (LFA-1)-, CD2- and CD28-costimulated T cell activation were also inhibited by TN, while TN could not affect the phorbol ester-stimulated T cell proliferation. Collectively, TN inhibits anti-CD3-induced T cell proliferation irrespectively of costimulatory molecules, suggesting that TN acts as a generally immunosuppressive extracellular matrix protein which potentially interferes with T cell receptor/CD3-mediated T cell activation.