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Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody
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 leukemi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890010/ https://www.ncbi.nlm.nih.gov/pubmed/27250643 http://dx.doi.org/10.1038/srep27150 |
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author | Sugata, Kenji Yasunaga, Jun-ichirou Miura, Michi Akari, Hirofumi Utsunomiya, Atae Nosaka, Kisato Watanabe, Yuko Suzushima, Hitoshi Koh, Ki-Ryang Nakagawa, Masanori Kohara, Michinori Matsuoka, Masao |
author_facet | Sugata, Kenji Yasunaga, Jun-ichirou Miura, Michi Akari, Hirofumi Utsunomiya, Atae Nosaka, Kisato Watanabe, Yuko Suzushima, Hitoshi Koh, Ki-Ryang Nakagawa, Masanori Kohara, Michinori Matsuoka, Masao |
author_sort | Sugata, Kenji |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4890010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48900102016-06-09 Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody Sugata, Kenji Yasunaga, Jun-ichirou Miura, Michi Akari, Hirofumi Utsunomiya, Atae Nosaka, Kisato Watanabe, Yuko Suzushima, Hitoshi Koh, Ki-Ryang Nakagawa, Masanori Kohara, Michinori Matsuoka, Masao Sci Rep Article 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. Nature Publishing Group 2016-06-02 /pmc/articles/PMC4890010/ /pubmed/27250643 http://dx.doi.org/10.1038/srep27150 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Sugata, Kenji Yasunaga, Jun-ichirou Miura, Michi Akari, Hirofumi Utsunomiya, Atae Nosaka, Kisato Watanabe, Yuko Suzushima, Hitoshi Koh, Ki-Ryang Nakagawa, Masanori Kohara, Michinori Matsuoka, Masao Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title | Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title_full | Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title_fullStr | Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title_full_unstemmed | Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title_short | Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody |
title_sort | enhancement of anti-stlv-1/htlv-1 immune responses through multimodal effects of anti-ccr4 antibody |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890010/ https://www.ncbi.nlm.nih.gov/pubmed/27250643 http://dx.doi.org/10.1038/srep27150 |
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