TCR zeta super(dim)lymphocytes define populations of circulating effector cells that migrate to inflamed tissues

• Published in: Blood 2007-05, Vol.109 (10), p.4328-4335
• Main Authors: Zhang, Zhuoli, Gorman, Claire L, Vermi, Anna-Chiara, Monaco, Claudia, Foey, Andrew, Owen, Sally, Amjadi, Parisa, Vallance, Alena, McClinton, Catherine, Marelli-Berg, Federica, Isomaeki, Pia, Russell, Andrew, Dazzi, Francesco, Vyse, Timothy J, Brennan, Fionula M, Cope, Andrew P
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-12-064170

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 super(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCR zeta super(bright) counterparts, TCR zeta super(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 super(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 super(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 super(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.