| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
We previously established a murine model for atopic dermatitis (AD), by repeated elicitation of contact hypersensitivity responses, in which many if not all of immunological alterations observed in the lesional skin of AD patients can be reproduced. Using this murine model, we investigated the mechanism for strong skewing of immune responses to type-2 cytokine production in AD patients : our previous studies showed that lymph node cells (LNC) in the acute phase were skewed toward type 1 cytokine production while those in the chronic phase were skewed toward type 2 cytokine production, a finding observed in AD lesions. In this study, we asked whether the strong skewing was due to the difference in the frequency of two distinct subsets, type 1 and type 2 T cells, or in the amount of cytokine produced per cell. T cells from the draining LN in the acute and chronic phases were analyzed for cytokine production by intracellular flow cytometric analyses. Unexpectedly, the acute and chronic LNC were found to contain equivalent frequencies of IFN-γ-producing CD8^+ and CD4^+ T cells. In contrast, the chronic LNC contained higher frequencies of IL-4-producing CD4^+ T cells, γδ^+ T cells, and NK cells than the acute LNC.This result clearly indicates that the decreased IFN-γ production seen in the chronic LNC was not due to lower frequencies of IFN-γ-producing T cells. Blocking of endogenous IL-4 and IL-10 by mAb only partially restored the ability of the chronic LNC to produce IFN-γ. In the chronic LNC, CD11c^+ dendritic cells (DC) capable of producing IL-12 were significantly decreased in frequencies. Thus, in the chronic LNC, many of IFN-γ-producing T cells would be silenced in situ by the combined effect of increased type 2 cells and decreased IL-12-producing DC.
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