title: Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells.
abstract: Naive antiviral CD8(+) T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs. Although CD8(+) T cells interact with both infected macrophages and DCs in the LN peripheral interfollicular region (PIR), DCs generate more frequent and stable interactions with T cells. VV infection induces rapid release of CCR5-binding chemokines in the LN, and administration of chemokine-neutralizing antibodies diminishes T cell activation by increasing T cell localization to macrophages in the macrophage-rich region (MRR) at the expense of PIR DCs. Similarly, DC ablation increases both T cell localization to the MRR and the duration of T cell-macrophage contacts, resulting in suboptimal T cell activation. Thus, virus-induced chemokines in DLNs enable antiviral CD8(+) T cells to distinguish DCs from macrophages to optimize T cell priming.
authors: Cell Biology and Viral Immunology Sections, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Heather D
authors: HD
authors: Hickman
authors: Lily
authors: L
authors: Li
authors: Glennys V
authors: GV
authors: Reynoso
authors: Erica J
authors: EJ
authors: Rubin
authors: Cara N
authors: CN
authors: Skon
authors: Jacqueline W
authors: JW
authors: Mays
authors: James
authors: J
authors: Gibbs
authors: Owen
authors: O
authors: Schwartz
authors: Jack R
authors: JR
authors: Bennink
authors: Jonathan W
authors: JW
authors: Yewdell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006651:Histocytochemistry; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019713:Receptors, CCR5 / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018925:Chemokines; D019713:Receptors, CCR5