Regulatory function of CpG-activated B cells in late-phase experimental allergic conjunctivitis.
OBJECTIVE
To determine how CpG, an immunostimulatory sequence, affects experimental allergic conjunctivitis and to determine the mechanisms of its action.


METHODS
Experimental allergic conjunctivitis was induced in mice to investigate the suppressive mechanism of CpG treatment. Cytokine profiling, fluorescence-activated cell sorting analyses, and adoptive transfer were used to analyze suppressive mechanisms after CpG treatment.


RESULTS
Administration of the CpG oligonucleotide induced significant splenomegaly. Adoptive transfer of the splenocytes isolated from CpG-treated mice was able to confer resistance to allergen-induced inflammatory responses in recipient mice. CpG treatment led to a transient upregulation of IL-1ra, IL-18, IL-1alpha, and IL-12 in the spleen, draining lymph nodes, and conjunctiva. In contrast, IL-10 showed a marked and sustained induction in the inductive and effector tissues. Splenomegaly after CpG exposure was reduced in IL-10-deficient mice, indicating that IL-10 is required for immune remodeling of the spleen. Analyses of allergen-sensitized mice deficient in IL-10 exacerbated the late-phase inflammatory responses. Fluorescence-activated cell sorting analysis of the CpG-induced splenocyte subsets showed that the predominant source of IL-10 was B220(+) CD19(+) CD23(+)IgM(+)CD40(+)class II(high) follicular B cells. Adoptive transfer of IL-10-deficient B cells exacerbated eosinophilia. Transfer of an expanded population of cells after CpG treatment, including IL-10-secreting follicular B cells, protected against eosinophilia.


CONCLUSIONS
CpG treatment provided B cell-mediated regulation of immune responses and B cell differentiation in CpG-induced immune remodeling with the use of IL-10.
Miyazaki
Dai
D
Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, 36-1 Nishicho Yonago, Tottori, Japan. dm@grape.med.tottori-u.ac.jp
Kuo
Chuan Hui
CH
Tominaga
Takeshi
T
Inoue
Yoshitsugu
Y
Ono
Santa Jeremy
SJ
D000085:Acetates; D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D031164:Ambrosia; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013163:Splenomegaly / Q000139:chemically induced / Q000276:immunology
D000085:Acetates; D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C401286:SWR 0342SA