Regulatory function of CpG-activated B cells in late-phase experimental allergic conjunctivitis.

Abstract

PURPOSE:

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.

• Authors: Dai Miyazaki, Chuan Hui Kuo, Takeshi Tominaga, Yoshitsugu Inoue, Santa Jeremy Ono
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 4 Pg. 1626-35 (Apr 2009) ISSN: 1552-5783 [Electronic] United States
• PMID: 19060266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Allergens
• CPG-oligonucleotide
• Cytokines
• Oligodeoxyribonucleotides
• RNA, Messenger
• SWR 0342SA

Topics

• Acetates
• Adoptive Transfer
• Allergens (immunology)
• Ambrosia
• Animals
• B-Lymphocytes (immunology)
• Conjunctivitis, Allergic (immunology, metabolism)
• Cytokines (genetics)
• Disease Models, Animal
• Female
• Flow Cytometry
• Hypersensitivity, Immediate (immunology)
• Lymphocyte Activation (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Oligodeoxyribonucleotides (pharmacology)
• Pollen (immunology)
• RNA, Messenger (metabolism)
• Spleen (cytology)
• Splenomegaly (chemically induced, immunology)