2000 Fiscal Year Final Research Report Summary
Selective Suppression of Pathogenic T Cell Responses Using Dendritic Cells
| Project/Area Number |
09307011
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Keio University |
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Principal Investigator |
IKEDA Yasuo Keio University, School of Medicine, Professor, 医学部, 教授 (00110883)
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| Co-Investigator(Kenkyū-buntansha) |
KUWANA Masataka Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50245479)
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| Project Period (FY) |
1997 – 2000
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| Keywords | dendritic cell / T cell / autoimmune disease / HLA / immunotherapy / immune thrombocytopenic purpura / scleroderma / antiphospholipid syndrome |
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| Research Abstract |
Dendritic cells (DC) are Antigen-presenting cells that are essential for initiation of T cell-dependent immunity, but distinct DC subsets are known to direct different classes of immune responses. Lymphoid DC precursors (pDC2) or plasmacytoid DC were recently identified as a human DC subset producing type I interferon and skewing Th2 responses. Here, we demonstrate that pDC2 isolated from human peripheral blood have a capacity to induce an anergic state in antigen-specific CD4^+ T cell lines. Tetanus toxoid (TT)-specific T cells incubated with TT-pulsed autologous pDC2 failed to proliferate in secondary cultures with optimal antigenic stimulation. T cell anergy induction required T cell receptor engagement with antigen/major histocompatibility complex presented on pDC2. The pDC2-induced unresponsiveness was completely or partially reversible in the presence of high-dose IL-2 in the secondary cultures. Autoreactive CD4^+ T cell clones specific for topoisomerase I derived from a patient with scleroderma were rendered anergic after coculture with topoisomerase I-pulsed autologous pDC2, resulting in failure to proliferate or provide help to B cells. These results suggest that pDC2 are involved in maintenance of peripheral T cell tolerance and have potential for use in the suppression of pathogenic T cell responses in autoimmune diseases and organ transplantation.
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