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Blood, 26 February 2009, Vol. 113, No. 9, pp. 1948-1956. Prepublished online as a Blood First Edition Paper on December 22, 2008; DOI 10.1182/blood-2008-02-139147. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-139147v1 113/9/1948    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 Sattler, A. Articles by Thiel, A. Search for Related Content PubMed PubMed Citation Articles by Sattler, A. Articles by Thiel, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 26, 2008 Accepted November 19, 2008 Cytokine-induced human IFN secreting effector-memory Th-cells in chronic autoimmune inflammation Arne Sattler, Ulf Wagner, Manuela Rossol, Joachim Sieper, Peihua Wu, Andreas Krause, Wolfgang A Schmidt, Sebastian Radmer, Siegfried Kohler, Chiara Romagnani, and Andreas Thiel* Clinical Immunology Group, German Rheumatism Research Centre, Berlin, Germany Department of Medicine IV, University of Leipzig, Leipzig, Germany Department of Rheumatology, Charite Campus Benjamin Franklin, Berlin, Germany Rheumaklinik Berlin-Buch, Berlin, Germany Immanuel Hospital, Berlin, Germany Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Regenerative Immunology and Aging, Berlin, Germany * Corresponding author; email: thiel{at}drfz.de. T-helper (Th)-cells activated by cytokines in the absence of T-cell receptor (TCR) ligation are suspected to participate in inflammatory processes by production of interferon gamma (IFN). Still, the relevance of such a mechanism has not been addressed in humans. Here we demonstrate that a subset of human effector-memory Th-cells expressing functional IL-12R, IL-18R and CCR5 ex vivo can be induced to secrete IFN by cytokines signalling via the IL-2R common -chain in combination with IL-12 and IL-18. Cytokine-driven IFN-production depends on JAK3- and p38 mitogen-activated kinase-signals and is sensitive to suppression by CD25++ regulatory T-cells. Contrary to IFN+ Th-cells induced upon antigen-specific stimulation, their cytokine-activated counterparts characteristically lack expression of costimulator 4-1BB (CD137). Strikingly, the vast majority of Th-cells infiltrating inflamed joints of Rheumatoid Arthritis patients is equipped with receptors prerequisite for cytokine-induced IFN-secretion. Amongst these cells, we detected a substantial fraction that secretes IFN directly ex vivo but lacks 4-1BB-expression, indicating that cytokine-induced IFN+ Th-cells operate in autoimmune inflammation. Our data provide a rationale for how human effector-memory Th-cells can participate in perpetuating inflammatory processes in autoimmunity even in the absence of TCR ligation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. F. Abreu, A. M. Grabiec, S. Krausz, R. Spijker, T. Burakowski, W. Maslinski, E. Eldering, P. P. Tak, and K. A. Reedquist The Presumed Hyporesponsive Behavior of Rheumatoid Arthritis T Lymphocytes Can Be Attributed to Spontaneous Ex Vivo Apoptosis rather than Defects in T Cell Receptor Signaling J. Immunol., July 1, 2009; 183(1): 621 - 630. [Abstract] [Full Text] [PDF]

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