Accuri C6 Flow Cytometer System
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0808505

Received for publication August 27, 2008.
Revised November 5, 2008.
Accepted for publication November 10, 2008.

Article

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

Jennifer L. Franko * and Alan D. Levine *{dagger}{ddagger}{sect}||@

Departments of *Pathology, {dagger}Medicine, {ddagger}Surgery, and {sect}Pharmacology and the ||Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

@ To whom correspondence should be addressed. E-mail: alan.levine{at}case.edu.


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Abstract

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.

Key Words: signal transduction • human • Rho-GTPases • filopodia • microspikes




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M. Gigoux, J. Shang, Y. Pak, M. Xu, J. Choe, T. W. Mak, and W.-K. Suh
Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
PNAS, December 1, 2009; 106(48): 20371 - 20376.
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