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HTLV-1

Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma

Leukemia volume 18, pages 126–132 (2004)Cite this article

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNγ in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.

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Acknowledgements

We are grateful to David Ghez, Lelia Delamarre and Ali Saib for critical reading of the manuscript. This work was supported by the Association de Recherche contre le Cancer (ARC) and the Fondation contre la Leucémie (Fondation de France). Bertrand Arnulf was the recipient of a Assistance Publique Hôpitaux de Paris (APHP) and a Centre National de la Recherche Scientifique (CNRS) Fellowships.

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Authors and Affiliations

  1. Service d'Hématologie and Centre National de la Recherche Scientifique, UMR 8603, Hôpital Necker, Paris, France

    B Arnulf & O Hermine

  2. Centre National de la Recherche Scientifique, UPR 9051, Institut Universitaire d'Hématologie, Hôpital St Louis, Paris, France

    M Thorel, Y Poirot & C Pique

  3. Laboratoire d'Immunologie et d'Histocompatibilité and Institut National de la Santé et de la Recherche Médicale, U396, Hôpital St Louis, Paris, France

    R Tamouza

  4. Département d'ImmunoHématologie Clinique, Hôpital St Louis, Paris, France

    E Boulanger & E Oksenhendler

  5. Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Limoges, Limoges, 87042, France

    A Jaccard

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Arnulf, B., Thorel, M., Poirot, Y. et al. Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma. Leukemia 18, 126–132 (2004). https://doi.org/10.1038/sj.leu.2403176

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