Fibronectin synthesis by activated T lymphocytes: up-regulation of a surface-associated isoform with signalling function

Fibronectin (FN) is a major constituent of the extracellular matrix. We now provide evidence for a surface-associated isoform of FN that is synthesized by T cells upon activation. The T-cell-derived FN has an unusual splice pattern: an additional domain, EDB, is produced whereas sequences within another domain, IIICS, are spliced out. CS1, the binding domain for very late antigen-4 (VLA-4), however, is still generated. To study the potential function of surface-associated FN its synthesis was down-regulated by an antisense oligonucleotide, then proliferation of T cells was induced by cross-linked anti-CD3. Proliferation was reduced as was expression of CD25. Moreover, when T cells were cultured in high density, the synthetic peptide QILDVPST, corresponding to CS1, inhibited proliferation, as did antibodies to VLA-4. We propose that surface-associated FN is a ligand for VLA-4, which by binding to VLA-4 on an adjacent cell, provides a costimulatory signal, thus sustaining T-cell proliferation.