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

Susan N. Thomas, Joseph M. Rutkowski, Miriella Pasquier, Emma L. Kuan, Kari Alitalo, Gwendalyn J. Randolph, Melody A. Swartz

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2181-2190
Number of pages10
JournalJournal of Immunology
Volume189
Issue number5
DOIs
StatePublished - Sep 1 2012

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Vascular Endothelial Growth Factor Receptor-3
Humoral Immunity
Drainage
Contact Dermatitis
T-Lymphocytes
Skin
Lymphatic Vessels
Lymph Nodes
Peripheral Tolerance
Langerhans Cells
Extracellular Fluid
Adaptive Immunity
Autoimmunity
Interleukin-4
Interleukin-10
Immunity
Immunization
Vaccination

ASJC Scopus subject areas

  • Immunology

Cite this

Thomas, S. N., Rutkowski, J. M., Pasquier, M., Kuan, E. L., Alitalo, K., Randolph, G. J., & Swartz, M. A. (2012). Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage. Journal of Immunology, 189(5), 2181-2190. https://doi.org/10.4049/jimmunol.1103545

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage. / Thomas, Susan N.; Rutkowski, Joseph M.; Pasquier, Miriella; Kuan, Emma L.; Alitalo, Kari; Randolph, Gwendalyn J.; Swartz, Melody A.

In: Journal of Immunology, Vol. 189, No. 5, 01.09.2012, p. 2181-2190.

Research output: Contribution to journalArticle

Thomas, SN, Rutkowski, JM, Pasquier, M, Kuan, EL, Alitalo, K, Randolph, GJ & Swartz, MA 2012, 'Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage', Journal of Immunology, vol. 189, no. 5, pp. 2181-2190. https://doi.org/10.4049/jimmunol.1103545
Thomas SN, Rutkowski JM, Pasquier M, Kuan EL, Alitalo K, Randolph GJ et al. Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage. Journal of Immunology. 2012 Sep 1;189(5):2181-2190. https://doi.org/10.4049/jimmunol.1103545
Thomas, Susan N. ; Rutkowski, Joseph M. ; Pasquier, Miriella ; Kuan, Emma L. ; Alitalo, Kari ; Randolph, Gwendalyn J. ; Swartz, Melody A. / Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage. In: Journal of Immunology. 2012 ; Vol. 189, No. 5. pp. 2181-2190.
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