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Journal of Virology, October 2004, p. 10320-10327, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10320-10327.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Direct Evidence for a Chronic CD8+-T-Cell-Mediated Immune Reaction to Tax within the Muscle of a Human T-Cell Leukemia/Lymphoma Virus Type 1-Infected Patient with Sporadic Inclusion Body Myositis

Simona Ozden,1 Madeleine Cochet,2 Jacqueline Mikol,3 Antonio Teixeira,4 Antoine Gessain,1 and Claudine Pique5*

Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes,1 URA CNRS 2581, Parasitology Department, Institut Pasteur,2 Service d'Anatomie et Cytologie Pathologiques, Hôpital Lariboisière,3 Service de Médecine Interne, Groupe Hospitalier Pitié-Salpêtrière,4 CNRS UPR 9051, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France5

Received 6 January 2004/ Accepted 21 May 2004

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4+ T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8+ T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4+ T cells and CD8+ T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.

* Corresponding author. Mailing address: CNRS UPR 9051, Hôpital St Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France. Phone: 33 1 53 72 40 95. Fax: 33 1 53 72 49 90. E-mail: pique{at}chu-stlouis.fr.

Journal of Virology, October 2004, p. 10320-10327, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10320-10327.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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