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 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

Successful Treatment of Protein-Losing Gastroenteropathy with Steroid Pulse and Immunosuppressive Therapies in a Patient with Sjögren Syndrome

We report the case of a 59-year-old female who developed facial edema together with hypoproteinemia. On the basis of 99mTc-human serum albumin scintigraphy and a1-antitrypsin clearance, she was diagnosed with protein-losing gastroenteropathy. Furthermore, she was diagnosed with Sjögren syndrome on the basis of eye and oral dryness, positive result with anti-SSA antibody, and salivary gland biopsy. Her symptoms improved with the use of immunosuppressive agents following steroid pulse therapy. Therefore, steroid pulse therapy and immunosuppressive agents should be considered as possible effective treatment strategies for protein-losing gastroenteropathy associated with autoimmune diseases

HTLV-1感染モデルとしてのニホンザルに自然感染しているサルT細胞白血病ウイルス1型の解析

京都大学0048新制・課程博士博士(医学)甲第18129号医博第3849号新制||医||1001(附属図書館)30987京都大学大学院医学研究科医学専攻(主査)教授 小柳 義夫, 教授 髙折 晃史, 教授 五十嵐 樹彦学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Michi Miura (2018) Wellcome Open Res. Data deposition - smFISH

Image data part of the publication "Epigenetics of HTLV-1

Michi Miura (2018) Wellcome Open Res. Data deposition - ChIP-seq

ChIP-seq data (.fastq.gz) part of the publication "Epigenetics of HTLV-1

A Single Protofilament Is Sufficient to Support Unidirectional Walking of Dynein and Kinesin

<div><p>Cytoplasmic dynein and kinesin are two-headed microtubule motor proteins that move in opposite directions on microtubules. It is known that kinesin steps by a ‘hand-over-hand’ mechanism, but it is unclear by which mechanism dynein steps. Because dynein has a completely different structure from that of kinesin and its head is massive, it is suspected that dynein uses multiple protofilaments of microtubules for walking. One way to test this is to ask whether dynein can step along a single protofilament. Here, we examined dynein and kinesin motility on zinc-induced tubulin sheets (zinc-sheets) which have only one protofilament available as a track for motor proteins. Single molecules of both dynein and kinesin moved at similar velocities on zinc-sheets compared to microtubules, clearly demonstrating that dynein and kinesin can walk on a single protofilament and multiple rows of parallel protofilaments are not essential for their motility. Considering the size and the motile properties of dynein, we suggest that dynein may step by an inchworm mechanism rather than a hand-over-hand mechanism.</p> </div