title: Induction of latency-associated peptide (transforming growth factor-β(1)) expression on CD4+ T cells reduces Toll-like receptor 4 ligand-induced tumour necrosis factor-α production in a transforming growth factor-β-dependent manner.
abstract: CD4(+) T cells expressing the latent form of transforming growth factor-β [latency-associated peptide (LAP) (TGF-β(1))] play an important role in the modulation of immune responses. Here, we identified a novel peptide ligand (GPC(81-95) ) with an intrinsic ability to induce membrane-bound LAP (TGF-β(1)) expression on a subpopulation of human CD4(+) T cells (using flow cytometry; ranging from 0·8% to 2·6%) and stimulate peripheral blood mononuclear cells to release LAP (TGF-β(1) ) (using ELISPOT assay; ranging from 0·03% to 0·16%). In spite of this low percentage of responding cells, GPC(81-95) significantly reduced Toll-like receptor 4 ligand-induced tumour necrosis factor-α production in a TGF-β(1) - and CD4(+) T-cell-dependent manner. The results demonstrate that GPC(81-95) is a useful tool to study the functional properties of a subpopulation of LAP (TGF-β(1))(+) CD4(+) T cells and suggest a pathway that can be exploited to suppress inflammatory response.
authors.affiliation: The Institute of Hepatology, University College London, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Boswell
authors.forename: Shayan
authors.initials: S
authors.lastname: Sharif
authors.forename: Akeel
authors.initials: A
authors.lastname: Alisa
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Pereira
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Shahriar
authors.initials: S
authors.lastname: Behboudi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D053673:Glypicans / Q000235:genetics; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053673:Glypicans; D008024:Ligands; D010455:Peptides; D011498:Protein Precursors; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C472416:latency-associated propeptide, TGF-beta