Get access

UV inhibits allergic airways disease in mice by reducing effector CD4+ T cells

Authors

  • J. P. McGlade,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
    • *Joint first authors.

  • D. H. Strickland,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
    • *Joint first authors.

  • M. J. M. Lambert,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • S. Gorman,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • J. A. Thomas,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • M. A. Judge,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • J. T. Burchell,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • G. R. Zosky,

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author
  • P. H. Hart

    1. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia
    Search for more papers by this author

Correspondence:
Dr P.H. Hart, Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, PO Box 855, West Perth, Western Australia 6872, Australia. E-mail: prueh@ichr.uwa.edu.au

Abstract

Background In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4+ effector cells at the airway mucosa orchestrate, and CD4+CD25+ regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues.

Objective To determine whether UV-induced changes in CD11c+ cells, CD4+CD25+ effector cells or CD4+CD25+ regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease.

Methods The phenotype and function of CD11c+ cells and CD4+CD25+ cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA.

Results No changes in the function of CD11c+ cells from UV-irradiated mice were observed. CD4+CD25+ cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4+ cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-β mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4+CD25+ cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10.

Conclusion Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4+CD25+ cells in the trachea and ADLNs, and not due to UV-induced regulatory cells.

Cite this as: J. P. McGlade, D. H. Strickland, M. J. M. Lambert, S. Gorman, J. A. Thomas, M. A. Judge, J. T. Burchell, G. R. Zosky and P. H. Hart, Clinical & Experimental Allergy, 2010 (40) 772–785.

Get access to the full text of this article

Ancillary