title: TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues.
abstract: 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.
authors.affiliation: Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom.
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.forename: Claire L
authors.initials: CL
authors.lastname: Gorman
authors.forename: Anna-Chiara
authors.initials: AC
authors.lastname: Vermi
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
authors.forename: Andrew
authors.initials: A
authors.lastname: Foey
authors.forename: Sally
authors.initials: S
authors.lastname: Owen
authors.forename: Parisa
authors.initials: P
authors.lastname: Amjadi
authors.forename: Alena
authors.initials: A
authors.lastname: Vallance
authors.forename: Catherine
authors.initials: C
authors.lastname: McClinton
authors.forename: Federica
authors.initials: F
authors.lastname: Marelli-Berg
authors.forename: Pia
authors.initials: P
authors.lastname: Isomäki
authors.forename: Andrew
authors.initials: A
authors.lastname: Russell
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Fionula M
authors.initials: FM
authors.lastname: Brennan
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cope
mesh_terms: D000328:Adult; D000818:Animals; D015535:Arthritis, Psoriatic / Q000097:blood / Q000276:immunology; D016918:Arthritis, Reactive / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D016466:CHO Cells; D002465:Cell Movement / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain