Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor.
Fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system whereas no proliferation was observed when CD4 cells were cultured with anti-CD3 alone or fibronectin alone. In addition, anti-CD29 (integrin beta 1) as well as anti-VLA-5 (human fibronectin receptor) antibodies blocked this CD4 cell activation in this system. Although anti-CD3 alone or fibronectin alone cannot induce IL-2 message by CD4 cells, the combination of anti-CD3 plus fibronectin induced IL-2 message by CD4 cells. In an analysis of the molecular mechanism by which IL-2 message was generated, we showed that a fibronectin-VLA-5 fibronectin receptor interaction may contribute an independent signal distinct from the CD3 pathway of activation by the induction of an AP-1 transcriptional factor. Thus the VLA-5 fibronectin receptor on CD4 cells can play a complementary role in CD3-TCR-mediated signal transduction through its interaction with fibronectin.
Yamada
A
A
Division of Tumor Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Nikaido
T
T
Nojima
Y
Y
Schlossman
S F
SF
Morimoto
C
C
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D005353:Fibronectins; D007376:Interleukin-2; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen; D014157:Transcription Factors; D011493:Protein Kinase C