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- Title
UV inhibits allergic airways disease in mice by reducing effector CD4<sup>+</sup> T cells.
- Authors
McGlade, J. P.; Strickland, D. H.; Lambert, M. J. M.; Gorman, S.; Thomas, J. A.; Judge, M. A.; Burchell, J. T.; Zosky, G. R.; Hart, P. H.
- 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.
- Publication
Clinical & Experimental Allergy, 2010, Vol 40, Issue 5, p772
- ISSN
0954-7894
- Publication type
Academic Journal
- DOI
10.1111/j.1365-2222.2010.03469.x