Induction of CD152 (CTLA-4) and LAP (TGF-β1) in human Foxp3− CD4+ CD25− T cells modulates TLR-4 induced TNF-α 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, GPC81-95, with the ability to induce both CD152 and LAP (TGF-β1) on human Foxp3− CD25− CD4+ T cells. The results demonstrate that GPC81-95 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 GPC81-95 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 GPC81-95 is a useful tool to study the functional properties of LAP (TGF-β1)+ CD152+ CD4+ T cells.