HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmidt-Supprian, M. Articles by Rajewsky, K. Search for Related Content PubMed PubMed Citation Articles by Schmidt-Supprian, M. Articles by Rajewsky, K.

IB Kinase 2 Deficiency in T Cells Leads to Defects in Priming, B Cell Help, Germinal Center Reactions, and Homeostatic Expansion¹

Marc Schmidt-Supprian^2,*, Jane Tian, Hongbin Ji, Cox Terhorst, Atul K. Bhan, Ethan P. Grant, Manolis Pasparakis^¶, Stefano Casola^*, Anthony J. Coyle and Klaus Rajewsky^*

^* CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115; Millennium Pharmaceuticals, Inc., Cambridge, MA 02139; Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Immunopathology Unit, Massachusetts General Hospital, Boston, MA 02114; and ^¶ European Molecular Biology Laboratory Mouse Biology Program, Monterotondo, Italy

Signal transduction from proinflammatory stimuli leading to NF-B-dependent gene expression is mediated by the IB kinase 2 (IKK2/IKK). Therefore, IKK2 has become an important drug target for treatment of inflammatory conditions. T cells, whose activation depends to a large extent on the activity of NF-B transcription factors, play important roles in inflammation and autoimmunity. Ablation of IKK2 specifically in T cells in CD4cre/Ikk2^FL mice allows their survival and activation by polyclonal stimuli in vitro, suggesting that IKK2 is dispensable for T cell activation. We report in this study that IKK2-deficient T cells expand efficiently in response to superantigen administration in vivo, but are completely deficient in recall responses, most likely due to inefficient priming. IKK2-deficient T cells provide suboptimal B cell help and fail to support germinal center reactions. Finally, IKK2 is essential for homeostatic expansion of naive T cells, reflected by the inability of IKK2-deficient T cells to induce colitis in lymphopenic hosts.

This article has been cited by other articles:

				L. Palkowitsch, J. Leidner, S. Ghosh, and R. B. Marienfeld Phosphorylation of Serine 68 in the I{kappa}B Kinase (IKK)-binding Domain of NEMO Interferes with the Structure of the IKK Complex and Tumor Necrosis Factor-{alpha}-induced NF-{kappa}B Activity J. Biol. Chem., January 4, 2008; 283(1): 76 - 86. [Abstract] [Full Text] [PDF]

				B. Greve, R. Weissert, N. Hamdi, E. Bettelli, R. A. Sobel, A. Coyle, V. K. Kuchroo, K. Rajewsky, and M. Schmidt-Supprian I{kappa}B Kinase 2/beta Deficiency Controls Expansion of Autoreactive T Cells and Suppresses Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2007; 179(1): 179 - 185. [Abstract] [Full Text] [PDF]