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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-01-0231. This Article Full Text (PDF) All Versions of this Article: 2002-01-0231v1 100/9/3287    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wysocka, M. Articles by Rook, A. H Search for Related Content PubMed PubMed Citation Articles by Wysocka, M. Articles by Rook, A. H Social Bookmarking                   What's this? Submitted January 24, 2002 Accepted June 13, 2002 Sezary syndrome patients demonstrate a defect in dendritic cell populations: Effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines Maria Wysocka, Mohamed H Zaki, Lars E French, Jihed Chehimi, Michael Shapiro, Suzanne E Everetts, Karen S McGinnis, Luis Montaner, and Alain H Rook* Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA, USA; The Wistar Institute, Philadelphia, PA, USA Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA, USA Department of Dermatology, Geneva University Hospital, Geneva, Switzerland The Wistar Institute, Philadelphia, PA, USA * Corresponding author; email: arook{at}mail.med.upenn.edu. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with involvement of the peripheral blood by malignant T cells. The disease is defined by impaired cell-mediated immunity, production of IFN and IL-2 possibly as a result of deficient IL-12 production. To understand the mechanism of this impairment, we examined the composition and function of dendritic cells and monocytes in the blood of SzS patients with different levels of peripheral blood tumor burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in normal volunteers. In contrast, decreased IL-12 production correlated with a decrease in the numbers of CD11c+ dendritic cells, which was particularly profound among medium (20-50% circulating malignant T cells) and high tumor burden patients (>50% circulating malignant T cells). Furthermore, CD123+ dendritic cells, major producers of IFN, were significantly diminished in SzS patients, regardless of the level of tumor burden. GM-CSF-treated patients experienced an increase in the number of dendritic cells but not in IFN or IL-12 production. However, in vitro stimulation of PBMC from SzS patients with rCD40L and IFN significantly increased production of IL-12. Thus, our results demonstrate a profound defect in circulating dendritic cells in SzS patients that may contribute to the pathogenesis of the cytokine disorders and to the depressed cellular immunity. Importantly, the ability of rCD40L to potently induce IL-12 production from monocytes and the residual dendritic cells of SzS patients could potentially serve as an immune restorative therapeutic agent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Wysocka, B. M. Benoit, S. Newton, L. Azzoni, L. J. Montaner, and A. H. Rook Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15 Blood, December 15, 2004; 104(13): 4142 - 4149. [Abstract] [Full Text] [PDF] A. K. De, K. Laudanski, and C. L. Miller-Graziano Failure of Monocytes of Trauma Patients to Convert to Immature Dendritic Cells is Related to Preferential Macrophage-Colony-Stimulating Factor-Driven Macrophage Differentiation J. Immunol., June 15, 2003; 170(12): 6355 - 6362. [Abstract] [Full Text] [PDF]

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