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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.

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IMMUNOBIOLOGY

TCR{zeta}dimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues

Zhuoli Zhang1, Claire L. Gorman1, Anna-Chiara Vermi1, Claudia Monaco1, Andrew Foey1, Sally Owen1, Parisa Amjadi1, Alena Vallance1, Catherine McClinton1, Federica Marelli-Berg2, Pia Isomäki1, Andrew Russell2, Francesco Dazzi2, Timothy J. Vyse2, Fionula M. Brennan1, and Andrew P. Cope1

1 Kennedy Institute of Rheumatology Division and 2 Division of Medicine, Faculty of Medicine, Imperial College London, United Kingdom

The T-cell receptor {zeta} (TCR{zeta}) chain is a master sensor and regulator of lymphocyte responses. Loss of TCR{zeta} 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{zeta} expression and effector function in T cells. We report here that TCR{zeta}dim lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCR{zeta}bright counterparts, TCR{zeta}dim cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCR{zeta}dim T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCR{zeta}dim T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCR{zeta}dim T cells make them promising cellular targets for the treatment of chronic inflammatory disease.


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