Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury

H Ishii,S Serada,T Yamashita,T Kubo,M Ueno,X Jin,S Tanabe,T Naka

doi:10.1038/cddis.2012.106

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.

Highlights

In the last decade, the improvement of motor function by adoptive transfer or activation of autoimmune T cells has been reported after CNS injury.[5,6,7,8,9,10]
These seemingly contradictory findings may be explained by the distinct roles of each T-lymphocyte subset; some are beneficial and others are detrimental to functional recovery after CNS injuries
IFN-g-producing type 1 helper T (Th1) cells and IL-17-producing helper T (Th17) cells are associated with the disease onset and progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.[17]

Summary

Introduction

In the last decade, the improvement of motor function by adoptive transfer or activation of autoimmune T cells has been reported after CNS injury.[5,6,7,8,9,10]. IFN-g-producing type 1 helper T (Th1) cells and IL-17-producing helper T (Th17) cells are associated with the disease onset and progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.[17] Shift to IL-4-producing type 2 helper T (Th2) cells was suggested to lead to enhanced functional recovery after CNS injury.[18] knowledge of the role played by each T-lymphocyte subset is still fragmental, and the effectiveness of transferring specific T lymphocytes to treat CNS injury remains unknown. We hypothesized that conflicting results concerning the role of T lymphocytes in recovery from CNS injury may be attributed to differences in the role of helper T-cell subsets, that the transfer of proinflammatory Th1 cells could facilitate functional recovery. We report that the transfer of Th1-conditioned cells, but not Th2- or Th17-conditioned cells, facilitated recovery of sensorimotor function after SCI

Methods

Results

Conclusion