Intravenous neural precursor cell (NPCs) injection attenuates experimental autoimmune encephalomyelitis by reducing autoreactive T cell encephalitogenicity in lymph nodes in vivo. Here we examined NPC-lymphocyte interactions in vitro. NPCs inhibited the induction of T cell activation marker IL-2-Receptor alpha, ICOS, PD-1 and CTLA-4 and inhibited T cell proliferation. NPCs inhibited T cell activation and proliferation in response to Concavalin-A and to anti-CD3/anti-CD28, which are T cell receptor (TCR)-mediated stimuli, but not in response to phorbol myristate acetate/ionomycin, a TCR-independent stimulus. The suppressive effect was not mediated via downregulation of CD3epsilon or induction of apoptosis. We next examined NPCs effects on inflammatory-cytokine signaling. NPCs impaired IL-2-mediated phosphorylation of JAK3 in lymphocytes, and inhibited IL-6 mediated proliferation of B9 murine hybridoma cells. In conclusion, NPCs ameliorate TCR-mediated T cell activation and inhibit inflammatory cytokines' signaling in immune cells. These findings may underlie the broad anti-inflammatory effects of NPCs in vivo.