Antigen-independent adhesion and cell spreading by inducible costimulator engagement inhibits T cell migration in a PI-3K-dependent manner.
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.
Franko
Jennifer L
JL
Department of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4952, USA.
Levine
Alan D
AD
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology*; D048430:Cell Shape / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011554:Pseudopodia; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D019869:Phosphatidylinositol 3-Kinases; D020742:rhoA GTP-Binding Protein