| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
The production of allergen-specific IgE in allergen-sensitized patients or animals has a mutual relation with the immunologic response leading to allergic rhinitis. We recently reported that after an intranasal (i.n.) injection of cedar pollen into mice, an IL-4-dependent increase in serum nonspecific IgE was a prerequisite for the production of serum allergen-specific IgE and that the submandibular lymph nodes were the main organ responsive to the i.n. injected allergen. After i.n. treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage (M)-and lymphocyte (L)-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the L-or M-rich population, produced significant amounts of IL-4, IgE, and IgG ; whereas the production was restored by the addition of Mac-1^+ cells in the M-rich fraction to the L-rich fraction. These results indicate that macrophages in the submandibular lymph nodes are essential not only for IL-4 or nonspecific Ig production but also for the class switching of Ig in lymphocytes in the initiation of allergic rhinitis.
The number of IgE^+ cells in the lymphoid tissues did not change significantly after an i.n., i.p., i.v. or s.c. injection of allergen into the mice, whereas a 2nd (s.c.) injection of the allergen into the i.v., but not into the i.n., i.p. or s.c., sensitized mice induced a small number of IgE^+/IgM^+/B220^+ B cells in the spleen. In contrast, the IgE+ cells were not seen in the blood or spleen of IL-4-/- mice after sensitization with the allergen. These results suggest that IgE+ basophils in the peripheral blood and IgE^+ B cells in the spleen might be IL-4-dependently induced as an indicator of sensitization with allergen and a precursor of cells secreting allergen-specific IgE antibody, respectively.
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