Modulation of murine experimental allergic conjunctivitis by treatment with alpha-galactosylceramide.
When mice are treated with alpha-galactosylceramide (alpha-GalCer), NKT cells are activated and suppress the development of experimental airway inflammation. This suppressive effect is believed to be mediated by the upregulation of IFN-gamma. Here, we investigated whether alpha-GalCer treatment can also modulate the development of experimental allergic conjunctivitis (EC). EC was induced in wild-type and IFN-gamma-deficient Balb/c mice by active immunization with ragweed (RW) followed by challenge with RW in eye drops. The mice were intraperitoneally injected with alpha-GalCer or vehicle at the time of immunization or before RW challenge. Twenty-four hours after RW challenge, conjunctivas, spleens and sera were harvested for histological analysis, flow cytometric, proliferation and cytokine assays, and measurement of immunoglobulin levels, respectively. Treatment with alpha-GalCer at the time of the EC-priming immunization significantly increased Th2 responses and markedly upregulated the severity of the EC. However, treatment with alpha-GalCer just before the Ag challenge that triggers EC in primed animals significantly suppressed the disease. This was associated with an increased frequency of CD4(+)CD25(+) cells, which express Foxp3, in the spleen. alpha-GalCer treatment just prior to Ag challenge also suppressed the development of EC in IFN-gamma-deficient mice, and we found apoptosis and anergy are unlikely to play a major role in the mechanism by which pre-challenge alpha-GalCer treatment suppresses EC. These data suggest that NKT cells can play a downregulatory role in the development of EC and that alpha-GalCer may be useful for treating allergic conjunctivitis.
Fukushima
Atsuki
A
Department of Ophthalmology and Visual Science, Kochi Medical School, Kohasu, Nankoku-City 783-8505, Japan. fukusima@med.kochi-u.ac.jp
Sumi
Tamaki
T
Fukuda
Ken
K
Yamaguchi
Tomoko
T
Kumagai
Naoki
N
Nishida
Teruo
T
Ueno
Hisayuki
H
D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000517:prevention & control*; D015536:Down-Regulation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011058:Pollen / Q000276:immunology
D000485:Allergens; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma