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Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells

K Emelie M Blomberg1*, Nicole Boucheron2, Jessica M Lindvall3, Liang Yu1, Julia Raberger2, Anna Berglöf1, Wilfried Ellmeier2 and CI Edvard Smith1*

Author Affiliations

1 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Huddinge, Sweden

2 Division of Immunobiology, Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria

3 Department for Informatics, Center for Bioinformatics, Post box 1080 Blindern NO-0316, Oslo, Norway

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BMC Genomics 2009, 10:233  doi:10.1186/1471-2164-10-233

Published: 18 May 2009



The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3+ T-cells, including CD4+ and CD8+ subsets, using Affymetrix microarrays.


The largest difference between Itk-/- and Wt CD3+ T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4+ and CD8+ T-cell subsets identified a greater differential expression than in total CD3+ cells. Cyclosporin A (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the Bub1, IL7R, Ctla2a, Ctla2b, and Schlafen1 genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found.


Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.