| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
As is well known in the case of Langerhans cells, dendritic cells (DCs) play a crucial role in the initiation of immunity to simple chemicals such as noted in the contact hypersensitivity. Since DCs are scattered in nonlymphoid organs as immature cells. They must be activated to initiate primary antigen specific immune reactions. Therefore, we hypothesized that some simple chemicals must affect the function of DCs. In this paper, we first demonstrated that human monocyte-derived DCs responded to such simple chemicals as DNCB, TNCB, DNFB, NiClィイD22ィエD2, MnClィイD22ィエD2, CoClィイD22ィエD2, SnClィイD22ィエD2, and CdSOィイD24ィエD2 by augmenting their expression of CD86 or HLA-DR antigen, down-regulating c-Fms expression or increasing their production of TNFα. In addition, the DCs stimulated with the chemicals demonstrated increased allogeneic T cell stimulatory function. Next, we found that, among these chemicals, only NiClィイD22ィエD2 and CoClィイD22ィエD2 induced apoptosis in them. Finally, we examined the effects of these chemicals on CD86 expression by 3 different macrophage subsets and DCs induced from the cultures of human peripheral blood monocytes in the presence of M-CSF, M-CSF + IL-4, GM-CSF, and GM-CSF + IL-4, respectively. Among them, only DCs dramatically augmented their expression of CD86. These observations have revealed unique characteristics of DCs which convert chemical stimuli to augmentation of their antigen presenting function, although their responses to different chemicals were not necessarily uniform in the phenotypic changes cytokine production or in the induction of apoptosis.
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