Development of Ntera2/D1 neurons as an alternative to embryonic neurons for transplantation therapy to ameliorate neurological deficits, currently in a Phase I trial for stroke symptoms, led to our discovery of a 40-60 kDA anionic protein with an isoelectric point of 4.8 expressed by these neurons that inhibits T-lymphocyte activation, suppresses the expression of interleukin 2 (IL-2), and blocks both naive and ongoing T-lymphocyte proliferation, which cannot be rescued by supplemental IL-2. Preliminary characterizations suggest that this neuron-derived protein represents a novel class of immunomodulators. We propose to purify and partially sequence this protein, perform a BLAST database search for sequence homology to establish that it is indeed a unique neuron-derived immunosuppressive protein (NIP), and test whether it abrogates specific T-lymphocyte mRNA and protein expressions of early phase and late phase activation cytokines and cell cycle regulatory genes and suppresses the effector functions of T-lymphocytes. Its identification will contribute to the development of therapies for preventing graft rejection in transplantation surgeries, for treating autoimmunities, and for preventing allergic reactions, will assist in determining whether Ntera2/D1 neuronal grafts are both therapeutic and self-protective, and will add to our understanding of the neuronal contribution to immune privilege within the central nervous system
