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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1387-1395. Prepublished online as a Blood First Edition Paper on November 13, 2007; DOI 10.1182/blood-2007-03-080648. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-080648v1 111/3/1387    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guihot, A. Articles by Carcelain, G. Search for Related Content PubMed PubMed Citation Articles by Guihot, A. Articles by Carcelain, G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Multicentric Castleman disease is associated with polyfunctional effector memory HHV-8–specific CD8+ T cells Amélie Guihot1, Eric Oksenhendler2, Lionel Galicier2, Anne-Geneviève Marcelin3, Laura Papagno1, Anne-Sophie Bedin1, Félix Agbalika4, Nicolas Dupin5, Jacques Cadranel6, Brigitte Autran1, and Guislaine Carcelain1 1 Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherché U 543, Université Pierre et Marie Curie Paris 6, Paris; 2 Département d'Immunologie Clinique, Hôpital Saint Louis, AP-HP, Paris; 3 Laboratoire de Virologie, Hôpital Pitié-Salpêtrière, AP-HP, EA 2387, Université Pierre et Marie Curie, Paris; 4 Laboratoire de Virologie, Hôpital Saint Louis, AP-HP, EA 3963, Université Paris 7, Paris; 5 Service de Dermatologie, Unité Propre de Recherche et de l'Enseignement Supérieur 1833, AP-HP, Hôpital Cochin, Paris; and 6 Service de Pneumologie, Hôpital Tenon, AP-HP, Paris, France Multicentric Castleman disease (MCD) is a devastating human herpesvirus 8 (HHV-8)–related lymphoproliferative disorder that occurs in immunocompromised persons. To determine the role of immune responses in MCD, we studied the frequency, antigenic repertoire, differentiation, and functional profile of HHV-8–specific CD8+ T cells in MCD patients and in human immunodeficiency virus–coinfected asymptomatic HHV-8 carriers (AC). Screening CD8+ T-cell responses with ELISpot interferon- (IFN-) assays using 56 peptides on 6 latent and lytic HHV-8 proteins showed that MCD and AC patients had responses of similar magnitude and antigenic repertoire and identified a new 10-mer human leukocyte antigen B7 CD8 epitope in K15. Intracellular IFN- staining showed significantly more CD45RA–CCR7–CD27– CD8+IFN-+ cells (late phenotype) and significantly fewer CCR7–CD27+CD45RA– cells (early and intermediate phenotype) in MCD than in AC patients. This phenotypic shift was not found for Epstein-Barr virus–specific CD8+ T cells tested as controls. HHV-8 viral loads were negatively correlated with early and intermediate effector memory cells. HHV-8–specific T cells were polyfunctional (secretion of IFN-, tumor necrosis factor-, macrophage inflammatory protein-1β, and/or CD107a) in both MCD and AC patients. In conclusion, MCD is not associated with a lack of HHV-8–specific CD8+ T cells or limitation of their functional profile. Their differentiation increases with HHV-8 viral load. These results offer new insight into the pathophysiology of MCD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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