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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 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 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 Sattler, A. Articles by Thiel, A. Search for Related Content PubMed PubMed Citation Articles by Sattler, A. Articles by Thiel, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Cytokine-induced human IFN-–secreting effector-memory Th cells in chronic autoimmune inflammation Arne Sattler1, Ulf Wagner2, Manuela Rossol2, Joachim Sieper3, Peihua Wu3, Andreas Krause4, Wolfgang A. Schmidt4, Sebastian Radmer5, Siegfried Kohler1, Chiara Romagnani1, and Andreas Thiel1,6 1 Clinical Immunology Group, German Rheumatism Research Centre, Berlin; 2 Department of Medicine IV, University of Leipzig, Leipzig; 3 Department of Rheumatology, Charité Campus Benjamin Franklin, Berlin; 4 Rheumaklinik Berlin-Buch, Berlin; 5 Immanuel Hospital, Berlin; and 6 Berlin-Brandenburg Center for Regenerative Therapies, Regenerative Immunology and Aging, Charité, Berlin, Germany T-helper (Th) cells activated by cytokines in the absence of T-cell receptor ligation are suspected to participate in inflammatory processes by production of interferon- (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 interleukin-12R (IL-12R), IL-18R, and CCR5 ex vivo can be induced to secrete IFN- by cytokines signaling 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 majority of Th cells infiltrating inflamed joints of rheumatoid arthritis patients is equipped with receptors prerequisite for cytokine-induced IFN- secretion. Among 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 Thcells can participate in perpetuating inflammatory processes in autoimmunity even in the absence of T-cell receptor 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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