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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 19, 2007 Accepted October 21, 2007 Multicentric Castleman disease is associated with polyfunctional effector memory HHV-8-specific CD8+ T cells Amelie Guihot, Eric Oksenhendler, Lionel Galicier, Anne-Genevieve Marcelin, Laura Papagno, Anne-Sophie Bedin, Felix Agbalika, Nicolas Dupin, Jacques Cadranel, Brigitte Autran, and Guislaine Carcelain* Laboratoire d'Immunologie Cellulaire, Hopital Pitie-Salpetriere, AP-HP, INSERM UMR S 543, Universite Pierre et Marie Curie Paris 6, Paris, France Departement d'Immunologie Clinique, Hopital Saint-Louis, AP-HP, Paris, France Laboratoire de Virologie, Hopital Pitie-Salpetriere, AP-HP, EA 2387, Universite Pierre et Marie Curie, Paris, France Laboratoire de Virologie, Hopital Saint Louis, AP-HP, EA 3963, Universite Paris 7, Paris, France Service de Dermatologie, UPRES 1833, AP-HP, Hopital Cochin, Paris, France Service de Pneumologie, Hopital Tenon, AP-HP, Paris, France * Corresponding author; email: guislaine.carcelain{at}psl.aphp.fr. Multicentric Castleman disease (MCD) is a devastating HHV-8 related lymphoproliferative disorder that occurs in immunocompromised individuals. 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 HIV-coinfected asymptomatic HHV-8 carriers (AC). Screening CD8+ T cell responses with ELISpot 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 HLA-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 EBV-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, TNF, MIP1, 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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