title: Transient Surface CCR5 Expression by Naive CD8+ T Cells within Inflamed Lymph Nodes Is Dependent on High Endothelial Venule Interaction and Augments Th Cell-Dependent Memory Response.
abstract: In inflamed lymph nodes, Ag-specific CD4(+) and CD8(+) T cells encounter Ag-bearing dendritic cells and, together, this complex enhances the release of CCL3 and CCL4, which facilitate additional interaction with naive CD8(+) T cells. Although blocking CCL3 and CCL4 has no effect on primary CD8(+) T cell responses, it dramatically impairs the development of memory CD8(+) T cells upon Ag rechallenge. Despite the absence of detectable surface CCR5 expression on circulating native CD8(+) T cells, these data imply that naive CD8(+) T cells are capable of expressing surface CCR5 prior to cognate Ag-induced TCR signaling in inflamed lymph nodes; however, the molecular mechanisms have not been characterized to date. In this study, we show that CCR5, the receptor for CCL3 and CCL4, can be transiently upregulated on a subset of naive CD8(+) T cells and that this upregulation is dependent on direct contact with the high endothelial venule in inflamed lymph node. Binding of CD62L and CD11a on T cells to their ligands CD34 and CD54 on the high endothelial venule can be enhanced during inflammation. This enhanced binding and subsequent signaling promote the translocation of CCR5 molecules from intracellular vesicles to the surface of the CD8(+) T cell. The upregulation of CCR5 on the surface of the CD8(+) T cells increases the number of contacts with Ag-bearing dendritic cells, which ultimately results in increased CD8(+) T cell response to Ag rechallenge.
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; dxa25@case.edu alex.y.huang@case.edu.
authors.forename: David
authors.identifier: 0000-0001-7272-2019
authors.initials: D
authors.lastname: Askew
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland OH 44195; and.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Su
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Barkauskas
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
authors.forename: R Dixon
authors.initials: RD
authors.lastname: Dorand
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Jay
authors.identifier: 0000-0003-2574-0438
authors.initials: J
authors.lastname: Myers
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Rachel
authors.initials: R
authors.lastname: Liou
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
authors.forename: Joseph
authors.identifier: 0000-0002-6506-8503
authors.initials: J
authors.lastname: Nthale
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 dxa25@case.edu alex.y.huang@case.edu.
authors.forename: Alex Y
authors.identifier: 0000-0002-5701-4521
authors.initials: AY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D040881:CD11a Antigen / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D007156:Immunologic Memory; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C000592874:CCR5 protein, mouse; D040881:CD11a Antigen; D019713:Receptors, CCR5; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin