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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4351-4359. Prepublished online as a Blood First Edition Paper on September 4, 2007; DOI 10.1182/blood-2007-01-070284. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-070284v1 110/13/4351    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 Davalos-Misslitz, A. C. M. Articles by Forster, R. Search for Related Content PubMed PubMed Citation Articles by Davalos-Misslitz, A. C. M. Articles by Forster, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 25, 2007 Accepted August 27, 2007 Impaired responsiveness to TCR stimulation and defective negative selection of thymocytes in CCR7-deficient mice Ana Clara Marques Davalos-Misslitz, Tim Worbs, Stefanie Willenzon, Gunter Bernhardt, and Reinhold Forster* Institute of Immunology, Hannover Medical School, Hannover, Germany * Corresponding author; email: foerster.reinhold{at}mh-hannover.de. The chemokine receptor CCR7 has been implicated in maintenance of thymus morphology and establishment of tolerance to self-antigens. Here, we provide direct evidence that negative selection of maturing thymocytes is defective in CCR7-deficent mice. Impaired negative selection was observed following TCR/CD3-complex stimulation in vivo as well as in vitro and was prominent in both double positive and semi-mature single positive cells (CD4+CD8-CD24high). Importantly, thymocytes of CCR7-/- mice display defective negative selection in response to endogenous superantigens, demonstrating that the defect also occurs under physiological conditions. Disturbed negative selection correlated with delayed activation kinetics and decreased calcium flux response of CCR7-/- thymocytes following in vitro TCR/CD3 stimulation, suggesting that an impaired response of CCR7-/- thymocytes via TCR-mediated signalling is responsible for defective negative selection in these mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Nitta, S. Nitta, Y. Lei, M. Lipp, and Y. Takahama CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens PNAS, October 6, 2009; 106(40): 17129 - 17133. [Abstract] [Full Text] [PDF] E. Ladi, T. A. Schwickert, T. Chtanova, Y. Chen, P. Herzmark, X. Yin, H. Aaron, S. W. Chan, M. Lipp, B. Roysam, et al. Thymocyte-Dendritic Cell Interactions near Sources of CCR7 Ligands in the Thymic Cortex J. Immunol., November 15, 2008; 181(10): 7014 - 7023. [Abstract] [Full Text] [PDF] T. M. McCaughtry, T. A. Baldwin, M. S. Wilken, and K. A. Hogquist Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla J. Exp. Med., October 27, 2008; 205(11): 2575 - 2584. [Abstract] [Full Text] [PDF]

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