LymphedemaV1, Main, Exploration, bibRecord, 004234

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

Identifieur interne : 004234 ( Main/Exploration ); précédent : 004233; suivant : 004235

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

Auteurs : Susan N. Thomas ; Joseph M. Rutkowski ; Miriella Pasquier ; Emma L. Kuan [États-Unis] ; Kari Alitalo [Finlande] ; Gwendalyn J. Randolph [États-Unis] ; Melody A. Swartz

Source :

Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2012.

RBID : PMC:3424306

Abstract

Lymphatic vessels transport interstitial fluid, soluble antigen, 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 antibody titers. In contrast, although delayed, T cell responses were robust after 21 days, including high levels of antigen-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. Additionally, one-year-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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424306

DOI: 10.4049/jimmunol.1103545
PubMed: 22844119
PubMed Central: 3424306

Affiliations:

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<front><div type="abstract" xml:lang="en"><p id="P1">Lymphatic vessels transport interstitial fluid, soluble antigen, 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 <italic>K14-VEGFR-3-Ig</italic>
 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, <italic>K14-VEGFR-3-Ig</italic>
 mice produced lower antibody titers. In contrast, although delayed, T cell responses were robust after 21 days, including high levels of antigen-specific CD8<sup>+</sup>
 T cells and production of IFN-γ, IL-4 and IL-10 upon restimulation. T cell-mediated CHS responses were strong in <italic>K14-VEGFR-3-Ig</italic>
 mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. Additionally, one-year-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.</p>
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Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

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