TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues.
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.
Zhang
Zhuoli
Z
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom.
Gorman
Claire L
CL
Vermi
Anna-Chiara
AC
Monaco
Claudia
C
Foey
Andrew
A
Owen
Sally
S
Amjadi
Parisa
P
Vallance
Alena
A
McClinton
Catherine
C
Marelli-Berg
Federica
F
Isomäki
Pia
P
Russell
Andrew
A
Dazzi
Francesco
F
Vyse
Timothy J
TJ
Brennan
Fionula M
FM
Cope
Andrew P
AP
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
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain