2000 Fiscal Year Final Research Report Summary
CHARACTERIZATION OF TCR Vβ REPERTOIRE AND TH1/TH2 CYTOKINE RELEASE OF TUMOR-SPECIFIC CYTOTOXIC T CELLS
| Project/Area Number |
09671340
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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 |
Digestive surgery
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| Research Institution | TOKYO WOMEN'S MEDICAL UNIVERSITY |
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Principal Investigator |
ARUGA Atsushi TOKYO WOMEN'S MEDICAL UNIVERSITY, DEPARTMENT OF GASTROENTEROLOGICAL SURGERY, ASSISTANT PROFESSOR, 医学部, 講師 (40221056)
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| Project Period (FY) |
1997 – 2000
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| Keywords | TCR Vβ / CTL / Dendritic cell / Cytokine / Immunotherapy |
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| Research Abstract |
In animal study, tumor-primed lymph node cells or splenocyte activated with tumor or anti-CD3 plus IL-2 mediated tumor regression in adoptive immunotherapy models and release tumor-reactive Type 1 cytokines in tumor specific manner. These cytotoxic T cells (CTL) consist of the several TCR Vβ subpopulations. The majority of the whole population were composed of Vβ3, 5, 7, 8 and 11+cells. TCR Vβ8+cells released high amounts of IFNγ with minimal amounts of IL-10 in response to tumor and mediated tumor regression in vivo. In contrast, TCR Vβ5, 7, 11+cells released low amounts of IFNγ with high level of IL-10 and had no in vivo antitumor reactivity. In human study, tumor-specific CTLs could be generated with tumor lysate or synthetic peptide-pulsed dendritic cells in vitro. These CTLs released high amount of IFNγ with minimal amounts of IL-10 and mediated tumor lysis in vitro cytotoxic assay. TCR Vβ usage of the patients with synthetic peptide-pulsed dendritic cell as cancer vaccine indicated the different profiles of TCR Vβ usage after vaccination. In this study, I demonstrated that Th1/Th2 cytokine patterns are expressed by immune T cells based upon TCR Vβ usage in mouse and human. Selective activation of effective Vβ subpopulation would be required for adoptive immunotherapy.
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Research Products
(17 results)
