| Project/Area Number |
14570417
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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 |
内科学一般
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
BABA Eishi KYUSHU UNIVERSITY, University Hospital, Research Associate, 大学病院, 助手 (00315475)
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| Co-Investigator(Kenkyū-buntansha) |
MORISAKI Takashi KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (90291517)
KATANO Mitsuo KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (10145203)
TANAKA Yuetsu Ryukyu University, Faculty of Medicine, Professor, 医学部, 教授 (30163588)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Tumor Immunoloav / T lymphocytes / Antigen presenting cells / OX40 / Intercellular molecular transfer / Dendritic cells / 癌ワクチン療法 |
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| Research Abstract |
Various immunotherapy against malignant tumors by using antigen presenting cells, such as monocytes-derived dendritic cells, had been examined. The present study was designed to analyze the mechanism of intercellular molecular transfer of OX40 between T lymphocytes and antigen presenting cells in order to improve the clinical efficacy of the immunotherapies. OX40/OX40L interaction was known to provide an important regulatory mechanism in both T cell-vascular endothelial cell adhesion and antigen-specific immune reactions. In this study, we showed that OX40, originally expressed on activated CD4^+ T cells, can be transferred to the cell surface of OX40L-expressing cells. In addition, we found that not only a 50 kDa authentic OX40 (p50) but also a 35 kDa OX40-related glycoprotein (p35 OX40rgp), which had altered glycosilations, were expressed on the surface of primary activated CD4^+ T cells and OX40-expressing cell lines. Intercellular transfer analysis showed that OX40L-dependent intercellular OX40-transfer occurs under physiological conditions, and that the transfer is possibly mediated by two istinct manners. We also analyzed the interaction between T lymphocytes and monocyte-derived dendritic cells obtained from malignant tumor patients who had autologous tumor lysate-pulsed dendritic cells therapy. Cancer patients were revealed to possess the subpopulation of monocyte-derived dendritic cell with impaired cell survival, cytokine production and antigen-presentation. These findings might provide information of the difficulties of immunotherapy for cancer patients.
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