UV inhibits allergic airways disease in mice by reducing effector CD4 T cells.
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-beta 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.


CONCLUSIONS
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.
McGlade
J P
JP
Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, West Perth, Western Australia, Australia.
Strickland
D H
DH
Lambert
M J M
MJ
Gorman
S
S
Thomas
J A
JA
Judge
M A
MA
Burchell
J T
JT
Zosky
G R
GR
Hart
P H
PH
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology*; D039521:CD11c Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis; D008198:Lymph Nodes / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000528:radiation effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects*; D014132:Trachea / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays; D000099192:CD69 Antigens
D000485:Allergens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039521:CD11c Antigen; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D010047:Ovalbumin; D000099192:CD69 Antigens; C508018:Il2ra protein, mouse