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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4328-4335. Prepublished online as a Blood First Edition Paper on January 25, 2007; DOI 10.1182/blood-2006-12-064170. This Article Full Text (PDF) All Versions of this Article: blood-2006-12-064170v1 109/10/4328    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 Zhang, Z. Articles by Cope, A. P Search for Related Content PubMed PubMed Citation Articles by Zhang, Z. Articles by Cope, A. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 20, 2006 Accepted January 16, 2007 TCRdim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues Zhuoli Zhang, Claire L Gorman, Anna-Chiara Vermi, Claudia Monaco, Andrew Foey, Sally Owen, Parisa Amjadi, Alena Vallance, Catherine McClinton, Federica M. Marelli-Berg, Pia Isomaki, Andrew Russell, Francesco Dazzi, Timothy J Vyse, Fionula M Brennan, and Andrew P Cope* The Kennedy Institute of Rheumatology Division, Imperial College, London, United Kingdom Division of Medicine, Imperial College, London, United Kingdom * Corresponding author; email: andrew.cope{at}imperial.ac.uk. The T cell receptor zeta (TCR) chain is a master sensor and regulator of lymphocyte responses. Loss of TCR expression has been documented in infectious, inflammatory and malignant diseases, suggesting that it may serve to limit T cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCR expression and effector function in T cells. We report here that TCRdim lymphocytes are enriched for antigen experienced cells refractory to TCR-induced proliferation. Compared to their TCRbright counterparts, TCRdim cells share characteristics of differentiated effector T cells but utilise accessory pathways for transducing signals for inflammatory cytokine gene expression, and cell contact dependent pathways to activate monocytes. TCRdim T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leucocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRdim T cells in peripheral blood, this T cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRdim T cells make them promising cellular targets for the treatment of chronic inflammatory disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. D. Isaacs Therapeutic T-cell manipulation in rheumatoid arthritis: past, present and future Rheumatology, May 25, 2008; (2008) ken163v1. [Abstract] [Full Text] [PDF] C. L. Gorman, A. I. Russell, Z. Zhang, D. Cunninghame Graham, A. P. Cope, and T. J. Vyse Polymorphisms in the CD3Z Gene Influence TCR{zeta} Expression in Systemic Lupus Erythematosus Patients and Healthy Controls J. Immunol., January 15, 2008; 180(2): 1060 - 1070. [Abstract] [Full Text] [PDF]

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