Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||Oita Medical University|
MOGI Goro Oita Medical University, vice president, 副学長 (20035190)
OKAMOTO Yoshitaka Yamanashi Medical University, Professor, 医学部, 教授 (40169157)
KIYONO Hiroshi Osaka University, Professor, 微生物病研究所, 教授 (10271032)
SUZUKI Masashi Oita Medical University, Professor, 医学部, 教授 (60211314)
KURONO Yuichi Kagoshima University, Professor, 医学部, 教授 (80153427)
KAWAUCHI Hideyuki Shimane Medical University, Professor, 医学部, 教授 (50161279)
|Project Period (FY)
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥23,500,000 (Direct Cost : ¥23,500,000)
Fiscal Year 1999 : ¥6,000,000 (Direct Cost : ¥6,000,000)
Fiscal Year 1998 : ¥17,500,000 (Direct Cost : ¥17,500,000)
|Keywords||NALT / Intranasal immunization / vaccine / Mucosal immune system / Haemophilus influenzae / Streptococcus pneumoniae / IgA / RS virue / 鼻粘膜 / 中耳粘膜 / マウス / CD4^+T細胞 / P6|
A. Experimental Study
1. Mucosal immune function of NALT
Selected Th2-type cytokine expressing CD4ィイD1+ィエD1 T cells were induced in intranasally-immunized mice NALT. M cells were observed in rat NALT. Antigen-specific IgA antibody titers in nasal wash were increased after immunization of mice without Peyers patches. These findings strongly suggest that NALT functions as an inductive site of nasal IgA response.
2. Induction of antigen-specific IgA by intranasal immunization in mice
The greatest antigen-specific IgA response was observed in mice intranasally immunized with P6, an antigen of nontypeable Haemophilus influenzae (NTHi) that is a major pathogen of otitis media. This response was induced not only in the nose but also in the middle ear. In mice immunized intranasally with fimbrial protein of Porhyromonas gingivalis, a causative agent for destructive chronic inflammation in the periodontium, antigen-specific IgA antibodies were induced in nasal mucosae and salivary glands. Thus, int
ranasal vaccination may be the most effective means for induction of antigen-specific mucosal immune responses in the upper respiratory tract.
3. Prevention of virus infection by intranasal immunization
Inflammatory reaction was mild in mice with Rs virus injected into the nasal cavity after intranasal immunization with vaccina virus. Nasal administrations of Fab antibodies against RS virus restricted viral proliferation and decreased the inflammatory reaction. These findings also lead us to the conclusion that intranasal immunization is useful for prevention of virus infection in the upper respiratory tract.
B. Clinical Study
1. The number of P6-specific IgA-secreting cells was greater in the tonsils showing no NTHi than in the samples with the bacteria. The number of P6-specific IgA-secreting cells in tonsils was correlated with IgA antibody titers in nasal secretions. Intratonsillar as well as intranasal immunization with OK-432 increased the number of M-protein-specific antibody-secreting cells in tonsils and antigen-specific antibody activity in nasal secretions. CD4ィイD1+ィエD1 T cells produced Th2-and Th1-type cytokines in response to stimulation with P6 or M-protein. These findings suggest that the palatine tonsils are important as an effector site.
2. Adenoid involvement in otitis media with effusion (OME)
NTHi was cultured more frequently in adenoids from patients with OME than in patients without OME. A tendency toward increased stratified squamous epithelium was apparent, and reticular epithelium extension was greater in patients with OME. The data suggest that adenoid inflammation is implicated in the pathogenesis of OME.
3. Antigen specific-antibody responses in otitis-prone children
Otitis-prone children exhibited reduced IgGィイD22ィエD2 responses to S. pneumoniae and IgG responses to NTHi. Otitis proneness appears to be related to numerous immunological deficiencies. Less