Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism

Martha J James, Lavina Belaramani, Kanella Prodromidou, Arpita Datta, Sussan Nourshargh, Giovanna Lombardi, Julian Dyson, Diane Scott, Elizabeth Simpson, Lorraine Cardozo, Anthony Warrens, Richard M Szydlo, Robert I Lechler, Federica M Marelli-Berg

    Research output: Contribution to journalArticlepeer-review

    28 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)2173-2179
    Number of pages7
    JournalBlood
    Volume102
    Issue number6
    Early online date29 May 2003
    DOIs
    Publication statusPublished - 15 Sept 2003

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