2016年6月2日
Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody.
Scientific reports
- 巻
- 6
- 号
- 開始ページ
- 27150
- 終了ページ
- 27150
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/srep27150
- 出版者・発行元
- NATURE PUBLISHING GROUP
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory diseases. Because anti-HTLV-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of HTLV-1-associated diseases. Using simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. The chemokine receptor CCR4 is expressed on STLV-1 infected cells, and administration of humanized monoclonal antibody to CCR4, mogamulizumab, dramatically decreased the number of STLV-1-infected cells in vivo. Concurrently, mogamulizumab treatment enhanced STLV-1 specific CD4(+) and CD8(+) T cell responses by simultaneously targeting CCR4(+) effector regulatory T (Treg) cells and infected cells. Mogamulizumab promoted the phagocytosis of CCR4(+) infected cells by macrophages, which likely enhanced antigen presentation. Vaccination with recombinant vaccinia virus (rVV) expressing viral antigens suppressed the proviral load and the number of Tax-expressing cells. Enhanced T-cell responses were also observed in some ATL patients who were treated with mogamulizumab. This study shows that mogamulizumab works not only by killing CCR4(+) infected cells directly, but also by enhancing T cell responses by increasing the phagocytosis of infected cells by antigen-presenting cells and suppressing CCR4(+) effector Treg cells.
- リンク情報
-
- DOI
- https://doi.org/10.1038/srep27150
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201702209404601378
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/27250643
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890010
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000376852500001&DestApp=WOS_CPL
- URL
- http://europepmc.org/abstract/med/27250643
- URL
- http://orcid.org/0000-0003-2166-6015
- ID情報
-
- DOI : 10.1038/srep27150
- ISSN : 2045-2322
- J-Global ID : 201702209404601378
- ORCIDのPut Code : 34012504
- PubMed ID : 27250643
- PubMed Central 記事ID : PMC4890010
- Web of Science ID : WOS:000376852500001