Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism.
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.
James
Martha J
MJ
Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Belaramani
Lavina
L
Prodromidou
Kanella
K
Datta
Arpita
A
Nourshargh
Sussan
S
Lombardi
Giovanna
G
Dyson
Julian
J
Scott
Diane
D
Simpson
Elizabeth
E
Cardozo
Lorraine
L
Warrens
Anthony
A
Szydlo
Richard M
RM
Lechler
Robert I
RI
Marelli-Berg
Federica M
FM
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
D018925:Chemokines; D018819:Dipeptidyl Peptidase 4