Central nervous system (CNS) infiltration of pro-inflammatory effector T cells is critical in the development and progression of multiple sclerosis. Here, Lim et al. develop a cationic cell-permeable peptide, dNP2, from the human novel LZAP-binding protein (NLBP), which efficiently delivered proteins into primary mouse and human immune cells in culture, and into the mouse brain in vivo. In mice, intraperitoneal injection of the peptide conjugated to the cytoplasmic domain of cytotoxic T lymphocyte antigen 4 (a T cell receptor with immune-suppressive function) inhibited T cell responses and ameliorated disease symptoms in experimental autoimmune encephalomyelitis.