| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
In 1998, we investigated dendritic cells (DC) in human superficial lymph nodes (LN). We found that lymph nodal DC can be classified into 3 groups. Namely, group I-DC is CD1a+/ CD83-/CD86- LC-type immature DC, group II-DC is CD1a-/CD83+/CD86+ mature IDC, and group III-DC is CD1a+/CD83-/CD86- stimulated IDC. Flow cytometric analysis indicated that the vast majority of DC obtained from the superficial LN were group-II DC. When group I-DC were cultured together with autologous lymph node T-cells, they matured into IDC. In addition, when immature DC were cultured with autologous LN T-cells in the presence of GM-CSF or IL-1, they matured into hyperplastic IDC resembling group-III IDC. These findings suggest that in superficial LN, LC-type DC are continuously provided from the skin, that they mostly undergo apoptosis without differentiating into IDC, and that this suppression takes place only in vivo. In 1999, we further investigated DC in the abdominal LN and found that they are much fewer t
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han those in the superficial LN, and that active changes of DC including migration, maturation and apoptosis may hardly take place in the gastrointestinal mucosa -LN system. We also investigated the maturation processes of DC taking advantage of the model of monocyte-derived DC (MoDC). We found that LC-type immature MoDC generated with GM-CSF+IL-4+TGF-b1 matured into IDC in autologous mixed leukocyte reaction (MLR), and that they mostly underwent apoptosis in allogenic MLR, although they strongly stimulated the proliferation of allogenic T-cells. Taken together, we hypothesize as follows ; (1) In superficial LN, a considerable number of LC-type immature DC are continuously provided from the skin, while they mostly undergo apoptosis without maturing into IDC. (2) T-cells promote these LC-type immature DC to mature into IDC antigen-nonspecifically. (3) Antigen-specific T-cells, which are stimulated with the antigens expressed on these DC, suppress their maturation into IDC, resulting in apoptosis of LC-type immature DC. (4) LC-type immature DC in LN have a opportunity to meet many T-cells specific for the antigens that they bare, because of the continuous circulation of T-cells, and antigen-activated T-cells remove them to avoid hyperimmunization. We consider that DC play a major role in immunological surveillance rather than strengthening and maintenance of immune responses. Less
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