Emergence of T Regulatory Cells Following Neural Precursor Cell Transplantation in Mouse Models of Multiple Sclerosis

Abstract

Abstract Multiple Sclerosis (MS) is a chronic, autoimmune disease of the central nervous system for which there is no cure. Defects in neurological function are a result of demyelination and axonal loss caused by infiltrating immune cells. Transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy to treat neurological diseases. However, studies evaluating NPC transplantation often employ a syngeneic donor or immune suppressed subjects. Therefore, it is important to consider how transplanted cells elicit an immune response. We report that human neural precursor cells (hNPCs) induce antigen specific Tregs which influence endogenous repair pathways to promote remyelination in murine models of MS. We observed remyelination and decreased neuroinflammation in mice receiving an intra-spinal transplant of syngeneic NPCs, which replaced damaged cells. Alternatively, mice receiving transplants of xenogeneic human NPCs displayed remyelination, a decrease in neuroinflammation, and an increase in CD4+CD25+FoxP3+ Tregs. Recovery was not a result of direct cell replacement as hNPCs underwent xenograft rejection. Importantly, ablation of Tregs abrogated histopathological improvement. Furthermore, hNPCs promoted generation of Tregs in vitro. These findings support an emerging role for Tregs in promoting tissue regeneration, distinct from immune modulation.