Identification of ingredients for suppressing HIV-1 replication by type-1 gamma-delta T cells
| Project/Area Number |
16K09262
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Hidemi Takahashi 日本医科大学, 大学院医学研究科, 大学院教授 (40221361)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 抗HIV薬 / 粘膜内HIV / NKT細胞 / Vγ1Vδ1型T細胞 / フラボノイド多糖体 / ケモカイン / 糖質フラボノイド / Vγ1Vδ1型γδT細胞 / フラボノイド / Vγ1Vδ1型Ｔ細胞 |
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| Outline of Final Research Achievements |
We established transfectants expressing T cell receptors (TCRs) for Vγ1 and Vδ1 (1C116) from the TCR-deficient line JRT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. The clone 1C116 is strongly stimulated by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring, through the Vγ1Vδ1 TCR. Additionally, hesperidin and linarin showed striking stimulatory activity for clone 1C116 to secrete IL-2 but also PBMC-derived T cells expressing Vγ1Vδ1 TCR; the activated Vγ1Vδ1 T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. The PBMC-derived Vγ1Vδ1 T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in both CD4+ NKT and CD4+ T cells. This is the first demonstration that flavonoid glycoside will activate functional Vγ1Vδ1 T cells to inhibit R5 tropic HIV-1 replication in CD4+ T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はこれまで、小腸粘膜内HIVが粘膜組織内のNKT細胞に潜伏感染したHIVが、治療の中断に伴い再活性化されること、そしてその再活性化の制御に粘膜内の１型γδ型Ｔ細胞が関与することを見いだして参りました。今回このγδ型Ｔ細胞を活性化しウイルスの再活性化を防ぐ物質が、枸杞のリナリンや陳皮のヘスペリジンに含まれるフラボノイド多糖体であることを見いだし、実際これら薬剤が１型γδ型Ｔ細胞を活性化しCD4陽性NKT細胞内のみならずCD4陽性T細胞内の、潜伏したHIV増殖を抑制することを見出しました。こうした研究成果は、今後のエイズ制圧治療のみならず、様々な抗ウイルス剤の開発に先鞭をつけるものであります。
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Anti-CD137 monoclonal antibody enhances trastuzumab-induced, natural killer cell-mediated cytotoxicity against pancreatic cancer cell lines with low human epidermal growth factor-like receptor 2 expression.2018
Author(s)
Takushi Masu, Masanori Atsukawa, Katsuhisa Nakatsuka, Masumi Shimizu, Daishu Miura, Taeang Arai, Hirotomo Harimoto, Chisa Kondo,縲?Keiko Kaneko, Seiji Futagami, Chiaki Kawamoto, Hidemi Takahashi, and Katsuhiko Iwakiri
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Journal Title
PLoS ONE
Volume: 13(12)
Issue: 12
Pages: e0200664-e0200664
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detection Method for Aquatic Bacteria of the Fingers, as a Potential Origin of the Aqueous Solution Contamination2017
Author(s)
Osono, E. Honda, K. Inoue, Y. Norose, Y. Takahashi, M. Ichimura, K. Kamano, C. Shinya, E. Takaku, S. Okamatsu, K. Kawamoto, S. Takizawa, H. Takahashi, H.
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Journal Title
Biocontrol Science
Volume: 22
Issue: 1
Pages: 61-65
DOI
NAID
ISSN
1342-4815, 1884-0205
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells.2016
Author(s)
Shinya, E., Shimizu, M., Owaki, A., Paoletti, S., Mori, L., De Libero, G., and Takahashi, H.
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Journal Title
Virology
Volume: 487
Pages: 285-295
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Effects of dendritic cell subset manipulation on airway allergy in a mouse model.2016
Author(s)
Murakami, R., Nakagawa, Y., Shimizu, M., Wakabayashi, A., Negishi, Y., Hiroi, T., Okubo, K., and Takahashi, H.
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Journal Title
Int. Arch. Allergy Immunol.
Volume: 168
Issue: 4
Pages: 219-232
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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