title: Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury.
abstract: The role of T lymphocytes in central nervous system (CNS) injuries is controversial, with inconsistent results reported concerning the effects of T-lymphocyte transfer on spinal cord injury (SCI). Here, we demonstrate that a specific T-lymphocyte subset enhances functional recovery after contusion SCI in mice. Intraperitoneal adoptive transfer of type 1 helper T (Th1)-conditioned cells 4 days after SCI promoted recovery of locomotor activity and tactile sensation and concomitantly induced regrowth of corticospinal tract and serotonergic fibers. However, neither type 2 helper T (Th2)- nor IL-17-producing helper T (Th17)-conditioned cells had such effects. Activation of microglia and macrophages were observed in the spinal cords of Th1-transfered mice after SCI. Specifically, M2 subtype of microglia/macrophages was upregulated after Th1 cell transfer. Neutralization of interleukin 10 secreted by Th1-conditioned cells significantly attenuated the beneficial effects by Th1-conditioned lymphocytes after SCI. We also found that Th1-conditioned lymphocytes secreted significantly higher levels of neurotrophic factor, neurotrophin 3 (NT-3), than Th2- or Th17-conditioned cells. Thus, adoptive transfer of pro-inflammatory Th1-conditioned cells has neuroprotective effects after SCI, with prospective implications in immunomodulatory treatment of CNS injury.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: S
authors.initials: S
authors.lastname: Tanabe
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Serada
authors.forename: T
authors.initials: T
authors.lastname: Naka
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001369:Axons / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009043:Motor Activity; D020933:Neurotrophin 3 / Q000378:metabolism; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014110:Touch
chemical_list: D020381:Interleukin-17; D020933:Neurotrophin 3; D016753:Interleukin-10