title: Induction of CD152 (CTLA-4) and LAP (TGF-β1) in human Foxp3- CD4+ CD25- T cells modulates TLR-4 induced TNF-α production.
abstract: CD152 (CTLA-4) is a co-stimulatory molecule that is expressed by T cells and negatively regulates immune responses. Here, we report the identification of a novel ligand, GPC(81-95), with the ability to induce both CD152 and LAP (TGF-β1) on human Foxp3(-) CD25(-) CD4(+) T cells. The results demonstrate that GPC(81-95) peptide-induced cell surface CD152 is endocytosed back into the cell during stimulation. The protein export and exocytosis of CD152 is also induced by this ligand. The inhibitory effects of GPC(81-95) on LPS-induced TNF-α production was shown to be closely associated with its ability to induce both LAP (TGF-β1) and CD152. Taken together, we have shown that a novel peptide ligand stimulates LAP (TGF-β1) and CD152 expression on resting CD4 T cells and have demonstrated that GPC(81-95) is a useful tool to study the functional properties of LAP (TGF-β1)(+) CD152(+) CD4(+) T cells.
authors: UCL Institute of Liver and Digestive Health, University College London, London, UK.
authors: Sandra
authors: S
authors: Boswell
authors: Ansar A
authors: AA
authors: Pathan
authors: Stephen P
authors: SP
authors: Pereira
authors: Roger
authors: R
authors: Williams
authors: Shahriar
authors: S
authors: Behboudi
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053673:Glypicans; D053645:Interleukin-2 Receptor alpha Subunit; D010446:Peptide Fragments; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha