title: TCR-driven transendothelial migration of human effector memory CD4 T cells involves Vav, Rac, and myosin IIA.
abstract: Human effector memory (EM) CD4 T cells may be recruited from the blood into a site of inflammation in response either to inflammatory chemokines displayed on or specific Ag presented by venular endothelial cells (ECs), designated as chemokine-driven or TCR-driven transendothelial migration (TEM), respectively. We have previously described differences in the morphological appearance of transmigrating T cells as well as in the molecules that mediate T cell-EC interactions distinguishing these two pathways. In this study, we report that TCR-driven TEM requires ZAP-70-dependent activation of a pathway involving Vav, Rac, and myosin IIA. Chemokine-driven TEM also uses ZAP-70, albeit in a quantitatively and spatially different manner of activation, and is independent of Vav, Rac, and mysosin IIA, depending instead on an as-yet unidentified GTP exchange factor that activates Cdc42. The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals.
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
authors: Thomas D
authors: TD
authors: Manes
authors: Jordan S
authors: JS
authors: Pober
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D009363:Neoplasm Proteins / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D018925:Chemokines; D009363:Neoplasm Proteins; D051567:Proto-Oncogene Proteins c-vav; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D051746:ZAP-70 Protein-Tyrosine Kinase; D019204:GTP-Binding Proteins; D024507:Nonmuscle Myosin Type IIA; D020744:rac GTP-Binding Proteins