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Antigen‐independent adhesion and cell spreading by inducible costimulator engagement inhibits T cell migration in a PI‐3K‐dependent manner
Author(s) -
Franko Jennifer L.,
Levine Alan D.
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0808505
Subject(s) - rhoa , filopodia , microbiology and biotechnology , cdc42 , cell migration , t cell , t cell receptor , biology , effector , rac1 , motility , cell adhesion , transfection , actin , cell , signal transduction , cell culture , immunology , immune system , biochemistry , genetics
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.