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.