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Open Access

HTLV-1-infected HIS Rag2-/-γc-/- mice, a suitable model for in vivo investigating the effects of drugs in ATL treatment?

  • Julien Villaudy1,
  • Anne Cachat1,
  • Sandrine Alais1,
  • Hiba El Hajj2,
  • Louis Gazzolo1,
  • Ghazi Zaatari3,
  • Olivier Hermine4,
  • Hughes de Thé5,
  • Ali Bazerbachi2 and
  • Madeleine Duc Dodon1Email author
Retrovirology20118(Suppl 1):A11

https://doi.org/10.1186/1742-4690-8-S1-A11

Published: 6 June 2011

Keywords

ArsenicInterferonZidovudineMesenteric Lymph NodeHuman Immune

Adult T cell Leukemia, an aggressive T-cell malignancy linked to HTLV-1 infection, is resistant to chemotherapy. Recently, promising results were obtained with the combination of arsenic trioxide, interferon alpha and zidovudine. However, the cellular and molecular mechanisms of their anti-leukemia activity remain to be investigated. To that aim, we have relied on HIS (Human Immune System) Rag2-/-γc-/- mice. We have indeed observed that when infected with HTLV-1, these mice displayed, five months later, an elevated number of human Tax-expressing T cells in the thymus, the spleen and the mesenteric lymph nodes. Some of them also developed T lymphoproliferative diseases.

To determine the effects of these three drugs on the apparition of these pathological features, Rag2-/-γc-/- mice were infected with HTLV-1 and, 16 weeks after infection, daily treated with the drugs for one week and sacrificed. Untreated HIS mice infected with HTLV-1 were used as control. Treatment resulted in a significant decrease in the spleen weight as compared to untreated controls. Interestingly, we also noted a decrease of the proviral load in thymocytes as well as a drop in the number of mature activated T cells in the spleen and in lymph nodes. These data clearly indicate that the HIS mouse model provides us with the opportunity not only for the pre-clinical evaluation of therapeutic approaches against the leukemogenic process associated with HTLV-1 infection, but also for unraveling the corresponding mechanisms.

Authors’ Affiliations

(1)
Virologie Humaine, INSERM U758, Ecole Normale Supérieure de Lyon, Lyon, France
(2)
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
(3)
Department of Pathology and laboratory Medicine, American University of Beirut, Beirut, Lebanon
(4)
CNRS UMR8603, Hôpital Necker, Paris, France
(5)
Université Diderot-Paris, Paris, France

Copyright

© Villaudy et al; licensee BioMed Central Ltd. 2011

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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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