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Blood, 1 January 2005, Vol. 105, No. 1, pp. 219-225. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-03-1055. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1055v1 105/1/219    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by French, L. E. Articles by Rook, A. H. Search for Related Content PubMed PubMed Citation Articles by French, L. E. Articles by Rook, A. H. Related Collections Immunobiology Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Impaired CD40L signaling is a cause of defective IL-12 and TNF- production in Sézary syndrome: circumvention by hexameric soluble CD40L Lars E. French, Bertrand Huard, Maria Wysocka, Ryan Shane, Emmanuel Contassot, Jean-François Arrighi, Vincent Piguet, Silvio Calderara, and Alain H. Rook From the Louis-Jeantet Skin Cancer Laboratory, Department of Dermatology, Geneva University Medical School, Switzerland; Apotech, Epalinges, Switzerland; and Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia. Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma characterized by peripheral blood involvement, impaired cell-mediated immunity, and T-helper 1 (TH1) cytokine production. To understand the mechanism of these defects, we studied the expression and function of CD40L in peripheral blood mononuclear cells (PBMCs) of patients with SzS. We found that PBMCs of patients with SzS have a defect in interleukin-12 (IL-12) and tumor necrosis factor- (TNF-) production upon anti-CD3 stimulation and that tumor CD4+ T lymphocytes have a specific defect in CD40L induction after anti-CD3 ligation in vitro. This defect may explain the poor IL-12 production, because IL-12 production by anti-CD3-stimulated PBMCs was dependent on CD40L in healthy donors. The observed defect in tumor cell CD40L expression appears to be due to inappropriate T-cell signaling upon CD3 ligation, because expression of other T-cell activation antigens such as CD25, and to a lesser extent CD69, are also impaired on tumor cells. Importantly however, the inability of SzS PBMCs to appropriately produce IL-12 and TNF- could be restored by recombinant hexameric CD40L. Taken together, our results demonstrate that impaired IL-12 and TNF- production in SzS is associated with defective CD4+ T lymphocyte CD40L induction and indicate that CD40L may have therapeutic potential in SzS. (Blood. 2005;105:219-225) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Casati, C. Camisaschi, L. Novellino, A. Mazzocchi, F. Triebel, L. Rivoltini, G. Parmiani, and C. Castelli Human Lymphocyte Activation Gene-3 Molecules Expressed by Activated T Cells Deliver Costimulation Signal for Dendritic Cell Activation J. Immunol., March 15, 2008; 180(6): 3782 - 3788. [Abstract] [Full Text] [PDF] S Serba, J Schmidt, N Wentzensen, E Ryschich, and A Marten Transfection with CD40L induces tumour suppression by dendritic cell activation in an orthotopic mouse model of pancreatic adenocarcinoma Gut, March 1, 2008; 57(3): 344 - 351. [Abstract] [Full Text] [PDF] G. Murugaiyan, R. Agrawal, G. C. Mishra, D. Mitra, and B. Saha Differential CD40/CD40L Expression Results in Counteracting Antitumor Immune Responses J. Immunol., February 15, 2007; 178(4): 2047 - 2055. [Abstract] [Full Text] [PDF] S. Hahtola, S. Tuomela, L. Elo, T. Hakkinen, L. Karenko, B. Nedoszytko, H. Heikkila, U. Saarialho-Kere, J. Roszkiewicz, T. Aittokallio, et al. Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma. Clin. Cancer Res., August 15, 2006; 12(16): 4812 - 4821. [Abstract] [Full Text] [PDF]

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