| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In 2002, I_studied the distribution, morphology, and immunophenotype of PDC in the human tonsil by immunofluorescent microscopy using monoclonal antibody CD123. The results indicated that PDC, which were identified as CD123+ lymphoid cells, were distributed in the T-cell area of the tonsil, especially around high endothelial venules (HEV). They coexpressed CD4, CD40, CD45RA, CD68, but not IDC-markers including CD83 and CD86. They were accumulated and formed large homotipic aggregates around HEV. PDC tended to be distributed separately from IDC, which were extensively dendriform cells positive for HLA-DR, CD83 and CD86. There was no cells showing features intermediate between PDC and IDC. On the contrary, PDC differentiated into IDC when cultured in the presence of IL-3 and CD40-ligand. These findings suggest that in the tonsil PDC have their own role and their differentiation into IDC was inhibited. In 2003, I precisely studied immunophenotype of IDC using S100b protein and fascin, and
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found that IDC are phenotypically heterogenous. IDC were classified into three subsets, S100b+ fascin-IDC (IDC-1), S100b+ fascin+ IDC (IDC-2), and S100b-fascin+ IDC (IDC-3). IDC-3 were morphologically different from S100b+ IDC (IDC-1 and IDC-2). Namely, IDC-1 tended to be larger and more dendritic in shape. Moreover, IDC-3 were stable, while IDC-1 and IDC-2 were unstable and tended to undergo apoptosis when cultured in vitro. We also found that numerous IDC-3 were present, while S100b+ IDC were scarce in histiocytic necrotizing, lymphadenitis (Kikuchi's disease). Insead of S100b+ IDC, numerous S100b+ T-cells, which expressed CD3 and CD8, were present around IDC-3. In contrast, there were a small number of IDC-3 and S100b+ T-cells in nonspecific lymphadenitis, tuberculous lymphadenitis, and sarcoidosis. These findings suggest that the origin of IDC-3 is different from the origin of S 100b+ IDC (IDC-1 and IDC-2). It is suggested that IDC-3 are derived from S100b-negative progenitors, while S100b+ IDC are derived from S100b+ progenitors. When PDC were cultured in the presence of CD40L, they differentiated into mature DC positive for CD83 and CD86, but negative for S100b, suggesting that S100b-negative IDC (IDC-3) are derived from PDC, while S100b+ IDC are derived from Langerhans cells and S100b+ T-cells. Less
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