Michi Miura
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Microbiology,
   Position   Instructor
Article types 原著
Language English
Peer review Peer reviewed
Title Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody.
Journal Formal name：Scientific reports
Abbreviation：Sci Rep
ISSN code：20452322/20452322
Domestic / ForeginForegin
Volume, Issue, Page 6,pp.27150
Author and coauthor 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
Publication date 2016/06
Summary 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.
DOI 10.1038/srep27150
PMID 27250643