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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1835. This Article Full Text (PDF) All Versions of this Article: 2002-06-1835v1 101/3/983    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 Andreakos, E. Articles by Feldmann, M. Search for Related Content PubMed PubMed Citation Articles by Andreakos, E. Articles by Feldmann, M. Social Bookmarking                   What's this? Submitted June 21, 2002 Accepted August 27, 2002 IB kinase 2 but not NF-B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction Evangelos Andreakos, Clive Smith, Claudia Monaco, Fionula M Brennan, Brian M Foxwell, and Marc Feldmann* Faculty of Medicine, Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, London, United Kingdom * Corresponding author; email: m.feldmann{at}ic.ac.uk. Although dendritic cells (DC) are the most potent antigen-presenting cells involved in numerous physiological and pathological processes, little is known about the signaling pathways that regulate DC activation and antigen-presenting function. Recently, we demonstrated that NF-B activation is central to that process as overexpression of IB blocks the allogeneic mixed lymphocyte reaction (MLR), an in vitro model of T cell activation. In this study, we investigated the role of two putative NF-B inducing components, NF-B-inducing kinase (NIK) and IB kinase 2 (IKK2). Using an adenoviral gene transfer method to efficiently express dominant negative (dn) forms of these molecules in monocyte-derived DC, we found that IKK2dn but not NIKdn inhibited the allogeneic MLR. When DC were fixed, this inhibitory effect of IKK2dn was lost suggesting that IKK2 is involved in T cell-derived signals that enhance DC antigen presentation during the allogeneic MLR period rather than an effect on viability or differentiation state of DC prior to coculture with T cells. One such signal is likely to be CD40 ligand (CD40L) as IKK2dn blocked CD40L but not LPS-induced NF-B activation, cytokine production and up-regulation of costimulatory molecules and HLA-DR in DC. In summary, our results demonstrate that IKK2 is essential for DC activation induced by CD40L or contact with allogeneic T cells, but not by LPS, whereas NIK is not required for any of these signals. In addition, our results support IKK2 as a potential therapeutic target for the down-regulation of unwanted immune responses that may occur during transplantation or autoimmunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. H. Y. Fong, M. Bebien, A. Didierlaurent, R. Nebauer, T. Hussell, D. Broide, M. Karin, and T. Lawrence An antiinflammatory role for IKK{beta} through the inhibition of "classical" macrophage activation J. Exp. Med., June 9, 2008; 205(6): 1269 - 1276. [Abstract] [Full Text] [PDF] A. M. Lundberg, S. K. Drexler, C. Monaco, L. M. Williams, S. M. Sacre, M. Feldmann, and B. M. 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