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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6112-6119.
Prepublished online as a Blood First Edition Paper on April 14, 2009; DOI 10.1182/blood-2008-07-170803.


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IMMUNOBIOLOGY

Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-{alpha} expression

Michelina Nascimbeni1,2,*, Leïla Perié1,2,*, Laurent Chorro1,2, Seckou Diocou1,2, Louis Kreitmann1,2, Stéphanie Louis1,2, Laurent Garderet3, Bettina Fabiani3, Anne Berger4, Jürgen Schmitz5, Jean-Pierre Marie6,7, Thierry Jo Molina8,9, Jérôme Pacanowski1,2, Jean-Paul Viard10, Eric Oksenhendler11, Stéphanie Beq12, Orly Abehsira-Amar1,2, Rémi Cheynier12, and Anne Hosmalin1,2

1 Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; 2 Inserm Unité 567, Paris, France; 3 Assistance Publique-Hôpitaux de Paris (AP-HP), Hématologie, Anatomie Pathologique, Hôpital Saint-Antoine, Paris, France; 4 AP-HP, Chirurgie Générale et Digestive, Hôpital Européen Georges Pompidou, Paris, France; 5 Miltenyi Biotec, Bergisch Gladbach, Germany; 6 Département d'Hématologie et d'Oncologie Médicale, AP-HP, Hôtel-Dieu, Paris, France; 7 Université Pierre et Marie Curie, Paris, France; 8 AP-HP, Hôtel-Dieu, Service d'Anatomie et Cytologie Pathologiques, Paris, France, 9 Université Paris Descartes, Paris, France; 10 AP-HP, Service des Maladies Infectieuses, Hôpital Necker, Paris, France; 11 AP-HP, Service d'Immunologie Clinique, Hôpital Saint-Louis, Paris, France; and 12 Département de Virologie, Institut Pasteur, Paris, France

We characterized the localization, phenotype, and some functions of plasmacytoid dendritic cells (pDCs) in the human spleen. pDCs were localized in the marginal zone and the periarteriolar region. Some were also found in the red pulp. pDCs were immature by phenotypic labeling, consistently with their capacity to internalize Dextran in a functional assay. In spleens from HIV-infected patients with thrombocytopenic purpura, these characteristics were unaffected. However, an accumulation of pDCs, but not myeloid dendritic cells (mDCs), was observed in some HIV+ patients, correlating with high proviral loads. Moreover, although undetectable in most HIV patients, interferon-{alpha} (IFN-{alpha}) production was evidenced in situ and by flow cytometry in most HIV+ patients. IFN-{alpha} was located in the marginal zone. Surprisingly, IFN-{alpha} colocalized only with few pDCs, but rather with other cells, including T and B lymphocytes, mDCs, and macrophages. Therefore, pDCs accumulated in spleens from HIV+ patients with high proviral loads, but they did not seem to be the main IFN-{alpha} producers.


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