Fibronectin synthesis by activated T lymphocytes: up‐regulation of asurface‐associated isoform with signalling function

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Abstract
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.