INHIBITION OF T-CELL ACTIVATION BY THE EXTRACELLULAR-MATRIX PROTEIN TENASCIN

Tenascin (TN) is an extracellular matrix protein that is expressed wid ely in the fetus and sparingly in the adult, but reappears at high lev els in certain areas of tissue insult such as tumor matrices and sites of wound healing. We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co-immobilized with the extracellular matrix protein fibronectin (FN). TN also inhibits prolif eration driven by alpha CD3/IL-2 or by phorbol ester/IL-2, and it prev ents high level induction of IL-2R. The presence of TN in culture medi um does not detectably alter the pattern of tyrosine phosphorylation r esulting from T cell triggering with alpha CD3, but at later time poin ts prevents the appearance oi functional NF-AT1 transcription factor c omplexes in T cell nuclear extracts. These findings are consistent wit h the postulated role for TN as a natural antagonist to FN action, and suggest that T cell responses occurring at tissue sites in which TN i s expressed could be influenced by its presence.