title: Selective diapedesis of Th1 cells induced by endothelial cell RANTES.
abstract: Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs.
authors.affiliation: Department of Immunology, The Forsyth Institute, Boston, MA 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: M
authors.initials: M
authors.lastname: Seki
authors.forename: K
authors.initials: K
authors.lastname: Hiromatsu
authors.forename: J W
authors.initials: JW
authors.lastname: Eastcott
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
authors.forename: M
authors.initials: M
authors.lastname: Sugai
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: M A
authors.initials: MA
authors.lastname: Taubman
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology; D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002999:Clone Cells; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology; D051381:Rats; D011923:Rats, Nude; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020741:rho GTP-Binding Proteins
chemical_list: D000199:Actins; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000941:Antigens; D018946:Chemokine CCL5; D007106:Immune Sera; D016169:Lymphocyte Function-Associated Antigen-1; D019713:Receptors, CCR5; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins