title: Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism.
abstract: Due to their ability to inhibit antigen-induced T-cell activation in vitro and in vivo, anergic T cells can be considered part of the spectrum of immunoregulatory T lymphocytes. Here we report that both murine and human anergic T cells can impair the ability of parenchymal cells (including endothelial and epithelial cells) to establish cell-cell interactions necessary to sustain leukocyte migration in vitro and tissue infiltration in vivo. The inhibition is reversible and cell-contact dependent but does not require cognate recognition of the parenchymal cells to occur. Instrumental to this effect is the increased cell surface expression and enzymatic activity of molecules such as CD26 (dipeptidyl-peptidase IV), which may act by metabolizing chemoattractants bound to the endothelial/epithelial cell surface. These results describe a previously unknown antigen-independent anti-inflammatory activity by locally generated anergic T cells and define a novel mechanism for the long-known immunoregulatory properties of these cells.
authors.affiliation: Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: James
authors.forename: Lavina
authors.initials: L
authors.lastname: Belaramani
authors.forename: Kanella
authors.initials: K
authors.lastname: Prodromidou
authors.forename: Arpita
authors.initials: A
authors.lastname: Datta
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Julian
authors.initials: J
authors.lastname: Dyson
authors.forename: Diane
authors.initials: D
authors.lastname: Scott
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Simpson
authors.forename: Lorraine
authors.initials: L
authors.lastname: Cardozo
authors.forename: Anthony
authors.initials: A
authors.lastname: Warrens
authors.forename: Richard M
authors.initials: RM
authors.lastname: Szydlo
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism*; D017635:Clonal Anergy / Q000276:immunology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D018819:Dipeptidyl Peptidase 4