title: Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage.
abstract: Lymphatic vessels transport interstitial fluid, soluble Ag, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower Ab titers. In contrast, although delayed, T cell responses were robust after 21 d, including high levels of Ag-specific CD8+ T cells and production of IFN-γ, IL-4, and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. In addition, 1-y-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity.
authors: Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne-EPFL, 1015 Lausanne, Switzerland.
authors: Susan N
authors: SN
authors: Thomas
authors: Joseph M
authors: JM
authors: Rutkowski
authors: Miriella
authors: M
authors: Pasquier
authors: Emma L
authors: EL
authors: Kuan
authors: Kari
authors: K
authors: Alitalo
authors: Gwendalyn J
authors: GJ
authors: Randolph
authors: Melody A
authors: MA
authors: Swartz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020405:Dermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004322:Drainage; D007108:Immune Tolerance / Q000235:genetics*; D056724:Immunity, Humoral / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D044148:Lymphatic Abnormalities / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D042601:Lymphatic Vessels / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D040321:Vascular Endothelial Growth Factor Receptor-3