| Co-Investigator(Kenkyū-buntansha) |
SHIBA Hiromi Shimane Medical Univ.Dept.of ORL,Assistant, 医学部, 助手 (30281760)
SANO Keisuke Shimane Medical Univ.Dept.of ORL,Assistant, 医学部, 助手 (10263542)
KATOH Taiji Shimane Medical Univ.Dept.of ORL,Assistant Prof., 医学部, 講師 (20185846)
片岡 真吾 島根医科大学, 医学部, 助手 (60152667)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Research Abstract |
For better understanding mechanism of nasal immune response, mucosal immunity of nasal mucosa was investigated in C57BL/6 and OVA-transgenic (OVA23-3) mice stimulated with repeated nasal challenge of antigen with cholera toxin (CT). Ag-specific IgA Ab titers against corresponding HRP or OVA antigens increased in nasal washings of CT-treated mice. In our immunochemistry, IgA-bearing B cells were found in nasal mucosa of mice with IgA Ab activity in nasal washings. In FACS analysis, CD3+T cells as well as B cells were harvested and alphabeta TCR+ T cells are found in a higher number in nasal mucosa, than saline-challenged control mice. gammadelta TCR+ T cells were also found. Semiquantitative analysis of cytokine gene expression by densitometer demonstrates that the expression of IFN-gamma, IL-2, and IL-6 was significaytly stronger in nasal lymphocytes of CT-treated mice, than in those of saline-challenged mice. These results might indicate that alphabeta TCR+ and gammadeltaTCR+ T cells
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play an important role for mounting and regulating IgA production of B cells in nasopharynx. A transfer study of human tonsillar lymphocytes into NOD-scid mice were successfully conducted in roder to examine the exact role of tonsilar lymphocytes as an inductive site of the immune response in peripheral mucosal sites such as nasopharynx and tubotympanum. Human leukocytes (CD45+), T cells (CD3+), and B cells (CD20+) are engrafted in the spleens and otehr non-lymphoid organ. In a flow cytometric analysis, human CD45+, CD3+, CD4+ (helper/inducer), CD8+ (suppressor/cytotoxic) cells were detected in various degrees in the spleens of NOD-scid mice at a 4-week interval after the intraperitoneal transfer. However, no engrAftment was seen in CB-17 scid mice. An immunostaining revealed that human leukocytes were present in the spleen, lung, and liver, but not in normal nasopharyngeal or tubotympanal mucosae. In NOD-scid mice engrafted with human tonsillar lymphocytes obtained from patients carrying alpha Streptococci, M-protein specific human IgG and IgA Ab activities were detected in the sera of these mice. Upon an intranasal immunization of M-protein with CT to these mice, M-protein specific human IgA antibody titers in nasal washings were higher than those of mice without the intransal challenge of M-protein. In an immunostaining, human T and B cells were recruited to the nasal mucosae around the nasopharyngeal lymphoreticular tissue (NALT) of those mice having higher human IgA Ab titers. These results may allow us to use this model as a promising tool for evaluating the lymphocyte homing and mechanism of the final differentiation of recruiting precurosr lymphocytes for mounting antien-specific immune response in peripheral mucosal sites of upper respiratory tract. Less
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