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The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta 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 TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(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. TCRzeta(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 TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.

Type

Journal

Blood

Publication Date

05/2007

Volume

109

Pages

4328 - 4335

Addresses

Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom.

Keywords

Lymphocyte Subsets, T-Lymphocytes, CHO Cells, Animals, Humans, Cricetulus, Arthritis, Reactive, Arthritis, Psoriatic, Arthritis, Rheumatoid, Inflammation, Membrane Proteins, Receptors, Antigen, T-Cell, Flow Cytometry, Transfection, Cell Movement, Fluorescence, Adult, Middle Aged, Cricetinae