Human T Cell Leukemia Virus Type I Expression in Salivary Glands of Infected Patients

Tangy, Frédéric; Ossondo, Marlène; Vernant, Jean‐Claude; Smadja, Didier; Blëtry, O.; Baglin, A.C.; Ozden, Simona

doi:10.1086/314588

Cited by 19 publications

(24 citation statements)

References 16 publications

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“…1G), consistent with previous observation of HTLV-1 expression in tissues of infected patients with inflammatory disorders (17,25,30). Although muscle cell cultures were carried out without mitogen, the number of tax mRNA-positive cells (Fig.…”

Section: Resultssupporting

confidence: 90%

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

Ozden¹,

Cochet

Mikol

et al. 2004

J Virol

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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-A‫20ء‬ 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.

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Section: Resultssupporting

confidence: 90%

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

Ozden¹,

Cochet

Mikol

et al. 2004

J Virol

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“…Such changes are strongly suspected to provide infected T lymphocytes with a highly motile phenotype. This observation could give an explanation for the broad distribution of infiltrated T lymphocytes and HTLV-1 proviral DNA in ATL and HAM/TSP patients who develop extraneural inflammatory disorders such as pulmonary alveolitis, dermatitis, Sjogren's syndrome, thyroid disease, uveitis, arthritis, and polymyositis (49)(50)(51)(52). In addition, as a microtubule organizer and cargo receptor, CRMP2 could be suspected to participate in HTLV-1 transmission via organization of the microtubule organizer center.…”

Section: Discussionmentioning

confidence: 99%

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

Varrin‐Doyer

Nicolle

Marignier

et al. 2012

The Journal of Immunology

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Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (CRMP2), a phosphoprotein involved in cytoskeleton rearrangement, in the control of human lymphocyte migration and in brain targeting in animal models of virus-induced neuroinflammation. Using lymphocytes cloned from infected patients and chronically infected T cells, we found that HTLV-1 affects CRMP2 activity, resulting in an increased migratory potential. Elevated CRMP2 expression accompanies a higher phosphorylation level of CRMP2 and its more pronounced adhesion to tubulin and actin. CRMP2 forms, a full length and a shorter, cleaved one, are also affected. Tax transfection and extinction strategies show the involvement of this viral protein in enhanced full-length and active CRMP2, resulting in prominent migratory rate. A role for other viral proteins in CRMP2 phosphorylation is suspected. Full-length CRMP2 confers a migratory advantage possibly by preempting the negative effect of short CRMP2 we observe on T lymphocyte migration. In addition, HTLV-1–induced migration seems, in part, supported by the ability of infected cell to increase the proteosomal degradation of short CRMP2. Finally, gene expression in CD69+ cells selected from patients suggests that HTLV-1 has the capacity to influence the CRMP2/PI3K/Akt axis thus to positively control cytoskeleton organization and lymphocyte migration. Our data provide an additional clue to understanding the infiltration of HTLV-1–infected lymphocytes into various tissues and suggest that the regulation of CRMP2 activity by virus infection is a novel aspect of neuroinflammation.

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“…Documented in vivo infection of noncultured adherent cells remains rare but has occasionally been reported in sweat gland epithelia (Setoyama et al, 1998(Setoyama et al, , 1999, salivary glands (Tangy et al, 1999), vascular endothelial cells (Setoyama et al, 1998) and mammary glands (Loureiro et al, 2000).…”

Section: Htlv-1 Tropism: In Vitro or In Vivo Veritas?mentioning

confidence: 99%

HTLV-1 tropism and envelope receptor

et al. 2005

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The identification of CD4 as the primary receptor for HIV followed shortly after the discovery of the virus, but the HTLV receptor remained long elusive, until its recent identification as the GLUT1 glucose transporter. In the present review, we describe the status of the literature that surrounded this discovery as well as the in vitro and in vivo observations that led to the identification of GLUT1. Also, we will explore a few tracks to conciliate the in vitro and in vivo data on HTLV-1 tropism within the context of the HTLV literature that has accumulated over the past 25 years. A close examination of these data leads us to conclude that the preferential detection of HTLV-1 in CD4 þ T lymphocyte subsets in vivo, even in the absence of leukemia, is not likely to be directly related to envelope receptor interactions, but rather to an array of postentry selection bottlenecks in vivo. Furthermore, we propose that infection of other hematopoietic and nonhematopoietic cells is likely to take place during the lifetime of an individual, with a burst early during the infection. Oncogene (2005) 24, 6016-6025.

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Human T Cell Leukemia Virus Type I Expression in Salivary Glands of Infected Patients

Cited by 19 publications

References 16 publications

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

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

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

HTLV-1 tropism and envelope receptor

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Human T Cell Leukemia Virus Type I Expression in Salivary Glands of Infected Patients

Cited by 19 publications

References 16 publications

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

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

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

HTLV-1 tropism and envelope receptor

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Product

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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

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