Volume 12 Supplement 1

17th International Confernce on Human Retroviruses: HTLV and Related Viruses

Open Access

HTLV-1 Tax induces Th1 master regulator T-bet and thus IFN-γ in CD4+CCR4+ T-cells of virus-associated myelopathy patients

  • Natsumi Araya1,
  • Tomoo Sato1,
  • Utano Tomaru2,
  • Ariella Coler-Reilly1,
  • Naoko Yagishita1,
  • Junji Yamauchi1,
  • Atsuhiko Hasegawa3,
  • Mari Kannagi3,
  • Hisanao Akiyama4,
  • Yasuhiro Hasegawa4,
  • Katsunori Takahashi1,
  • Yasuo Kunitomo1,
  • Yuetsu Tanaka5,
  • Atae Utsunomiya6,
  • Steven Jacobson7 and
  • Yoshihisa Yamano1Email author
Retrovirology201512(Suppl 1):P44

https://doi.org/10.1186/1742-4690-12-S1-P44

Published: 28 August 2015

The plasticity inherent to the CD4+ T cell differentiation program especially as it pertains to regulatory T (Treg) cells has been implicated in the pathogeneses of multiple inflammatory diseases. Human T-lymphotropic virus type 1 (HTLV-1) is thought to effect transcriptional changes in infected T cells via HTLV-1 Tax that can cause once suppressive CD4+CD25+CCR4+ Treg cells to lose FOXP3 expression and produce IFN-γ. We hypothesized that spawning of such inflammatory Th1-like cells from infected CCR4+ T cells plays a key role in the pathogenesis of the neurodegenerative inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this study, we demonstrated that Tax in cooperation with specificity protein 1 (Sp1) boosts the expression of the Th1 master regulator T box transcription factor (T-bet/Tbx21) and consequently IFN-γ. We established the presence of abundant CD4+CCR4+ T cells co-expressing the Th1 marker CXCR3 and producing T-bet/Tbx21 and IFN-γ in the CSF and spinal cord lesions of HAM/TSP patients. Finally, we tested treatments on ex vivo cell cultures from patients and found evidence that a therapy targeting CCR4+ T cells via antibody-dependent cellular cytotoxicity may represent a viable treatment option for HAM/TSP.

Authors’ Affiliations

(1)
Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine
(2)
Department of Pathology, Hokkaido University Graduate School of Medicine
(3)
Department of Immunotherapeutics, Tokyo Medical and Dental University, Graduate School
(4)
Department of Neurology, St. Marianna University School of Medicine
(5)
Department of Immunology, Graduate School of Medicine, University of the Ryukyus
(6)
Department of Hematology, Imamura Bun-in Hospital
(7)
Viral Immunology Section, Neuroimmunology Branch, National Institutes of Health

Copyright

© Araya et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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