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.
Wagner
C
C
Institut für Immunologie, Universität Heidelberg, Heidelberg, Germany.
Bürger
A
A
Radsak
M
M
Blum
S
S
Hug
F
F
Hänsch
G M
GM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004768:Enterotoxins; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016376:Oligonucleotides, Antisense; D010835:Phytohemagglutinins; D020033:Protein Isoforms; D016201:Receptors, Lymphocyte Homing; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal