IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells.
BACKGROUND
Allergic rhinitis is one of the most common allergic inflammatory diseases characterized by a predominant TH2 response with antigen-specific IgE synthesis. IL-15 plays important roles in activation and maintenance of memory CD8+T cells capable of producing IFN-gamma, which regulates TH2 responses.


OBJECTIVE
To investigate the roles of endogenous IL-15 in allergic inflammation, we examined allergic rhinitis in IL-15 knockout (KO) mice sensitized with ovalbumin followed by intranasal rechallenge with ovalbumin.


METHODS
IL-15KO mice were sensitized intraperitoneally with ovalbumin/complete Freund's adjuvant on day 0 and ovalbumin/IFA on day 7, and then were intranasally challenged with ovalbumin on days 21, 22, 23, 24, and 25. Nasal symptoms and histologic changes were examined. IgE production and TH2 responses were measured by ELISA. Purified CD8+T cells or recombinant IL-15 were administered into ovalbumin-sensitized mice.


RESULTS
The levels of IgE production and TH2 responses in IL-15KO mice were comparable to those in control mice after ovalbumin sensitization. However, sneezing, infiltration of eosinophils into the nasal mucosa, and TH2 cytokine production were aggravated in ovalbumin-sensitized IL-15KO mice after intranasal challenge with ovalbumin. Adoptive transfer of CD8+6 T cells from ovalbumin-sensitized mice suppressed the TH2 responses in mice but not in IL-15KO mice. Administration of IL-15 with ovalbumin significantly prevented the development of allergic rhinitis in ovalbumin-sensitized mice.


CONCLUSIONS
We demonstrate with IL-15KO mice that endogenous IL-15 plays an important role in suppression of allergic rhinitis at effector phase. Intranasal administration of IL-15 is useful as a therapeutic approach to control allergic rhinitis.


CONCLUSIONS
Intranasal administration of recombinant IL-15 might become new immunotherapy for allergic rhinitis.
Aoi
Noriaki
N
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Shimane University, Izumo, Japan.
Masuda
Tokuko
T
Murakami
Daisuke
D
Yajima
Toshiki
T
Mizubuchi
Hiroyuki
H
Yamada
Hisakata
H
Kawauchi
Hideyuki
H
Yoshikai
Yasunobu
Y
D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D019409:Interleukin-15 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*
D018984:Epitopes, T-Lymphocyte; D019409:Interleukin-15; D010047:Ovalbumin