Antigen-independent adhesion and cell spreading by inducible costimulator engagement inhibits T cell migration in a PI-3K-dependent manner

J Leukoc Biol. 2009 Mar;85(3):526-38. doi: 10.1189/jlb.0808505. Epub 2008 Dec 18.


Engagement of the costimulatory protein ICOS activates effector/memory T cells in tissue by enhancing TCR-mediated proliferation and cytokine production. We now report that in an antigen-independent manner, ICOS also induces adhesion and spreading in human effector/memory T cells, consequently inhibiting cell migration. T cell spreading and elongation after ICOS ligation are accompanied by the formation of two types of actin-rich membrane protrusions: thin, finger-like structures similar to filopodia and short, discrete microspikes. Although filopodia/microspike formation occurs independently of the PI-3K signaling cascade, ICOS-mediated T cell elongation depends on PI-3K activity, which inhibits the accumulation of GTP-bound RhoA. Further inhibition of RhoA activation exacerbates the ICOS-mediated, elongated phenotype. We propose that in inflamed tissue, ICOS engagement by ICOS ligand on a professional or nonprofessional APC prevents the forward motility of the T cell by inhibiting RhoA-dependent uropod retraction. The resulting ICOS-induced T cell spreading and filopodia/microspike formation may promote antigen recognition by enhancing a T cell's scanning potential of an adherent APC surface.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • Cell Adhesion / immunology*
  • Cell Shape / immunology
  • Cells, Cultured
  • Chemotaxis, Leukocyte*
  • Humans
  • Immunologic Memory
  • Inducible T-Cell Co-Stimulator Protein
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pseudopodia
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • rhoA GTP-Binding Protein / physiology


  • Antigens, Differentiation, T-Lymphocyte
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Phosphatidylinositol 3-Kinases
  • rhoA GTP-Binding Protein