2005 Fiscal Year Final Research Report Summary
A Study of Activation and Apoptosis of Peripheral Blood Mononuclear Cells and Lamina Propria Mononuclear Cells in Inflammatory Bowel Diseases
| Project/Area Number |
16590586
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya University |
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Principal Investigator |
ANDO Takafumi Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80378041)
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| Co-Investigator(Kenkyū-buntansha) |
NIWA Yasumasa Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20283442)
OHMIYA Naoki Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (00335035)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Inflammatory bowel diseases / lamina propria mononuclear cells / CD4-positive T cells / apoptosis / anti-cytokine therapy / anti-TNF-alpha antibody / prediction of treatment efficacy |
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| Research Abstract |
Peripheral blood mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) were isolated from the peripheral venous blood and the surgical specimens, respectively, by 6% dextran sedimentation followed by density gradient centrifugation on Ficoll-Hypaque. From PBMCs and LPMCs, CD4-positive T cells were isolated using magnetic cell sorting. Flow cytometric analysis confirmed that isolated CD4-positive T cells were very pure (PBMCs: 99.0±0.3%, LPMCs: 98.5±0.4%). CD4-positive T cells were cultured in microwell plates coated with anti-CD3 and anti-CD28 antibodies. The expression of IL-2 receptor (IL-2R) alpha chain and membranous type TNF-alpha mRNA were peaked after 96h in CD4-positive T cells from either PBMCs or LPMCs. Both IL-2R and TNF-alpha mRNA expressions were detected more commonly in CD4-positive T cells from LPMCs compared with CD4-positive T cells from PBMCs. A chimeric anti-TNF-alpha antibody (infliximab) has induced apoptosis on CD4-positive T cells, which indicat
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es that it might be possible to predict the efficacy of drugs before treatment in vitro. Thirteen patients with Crohn's Disease were treated with infliximab. Clinical response was evaluated using the Crohn's Disease Activity Index (CDAI), and serum soluble IL-2 receptor (sIL-2 R), IL-6, and TNF-alpha levels were analyzed by ELISA before and after treatment. Apoptosis of peripheral and lamina propria T-lymphocytes after culture with infliximab was detected by flow cytometry. CDAI and serum sIL-2 R, IL-6 and TNF-alpha levels decreased in most patients after treatment with infliximab. Serum TNF-alpha levels before treatment in the six patients in whom CDAI decreased by more than 70 were less than 5 ng/ml. Infliximab induced the apoptosis of lamina propria but not peripheral T-lymphocytes. A low level of serum TNF-alpha might be an indicator for infliximab treatment. The induction of apoptosis of lamina propria T-lymphocytes by anti-cytokine drugs may be one of the important mechanisms of their anti-inflammatory effect in patients with inflammatory bowel disease. Less
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Research Products
(10 results)
