title: T cell deficiency in spinal cord injury: altered locomotor recovery and whole-genome transcriptional analysis.
abstract: BACKGROUND
  T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T cell-deficient athymic nude (AN) rats exhibit improved functional recovery when compared to immunocompetent Sprague-Dawley (SD) rats following spinal cord transection.
  
  
  METHODS
  In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery.
  
  
  RESULTS
  Athymic nude rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for T(h)2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. Immunostaining for macrophage markers revealed no T cell-dependent difference in the acute macrophage infiltrate.
  
  
  CONCLUSIONS
  We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue.
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. satz0002@umn.edu.
authors.forename: David
authors.initials: D
authors.lastname: Satzer
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. mill5459@umn.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Miller
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. maxon004@umn.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Maxon
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. vothx042@umn.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Voth
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. dibar002@umn.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: DiBartolomeo
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. mahon212@umn.edu.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mahoney
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. dutto015@umn.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Dutton
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. lowwalt@umn.edu.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.affiliation: Department of Neurosurgery, University of Minnesota, D429 Mayo Memorial Building, MMC 96, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA. amparr@umn.edu.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. amparr@umn.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Parr
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016923:Cell Death / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D008124:Locomotion / Q000502:physiology*; D009474:Neurons / Q000276:immunology*; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*