Induction of CD152 (CTLA-4) and LAP (TGF-beta 1) in human Foxp3(-) CD4(+) CD25(-) T cells modulates TLR-4 induced TNF-alpha production

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-beta 1) 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-alpha production was shown to be closely associated with its ability to induce both LAP (TGF-beta 1) and CD152. Taken together, we have shown that a novel peptide ligand stimulates LAP (TGF-beta 1) and CD152 expression on resting CD4T cells and have demonstrated that GPC(81-95) is a useful tool to study the functional properties of LAP (TGF-beta 1)(+) CD152(+) CD4(+) T cells.