Abstract
BackgroundT 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.MethodsIn 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.ResultsAthymic 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 Th2 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0212-0) contains supplementary material, which is available to authorized users.
Highlights
T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process
Systemic spread of central nervous system (CNS) antigens after SCI leads to the formation of autoimmune T cells [3, 4] that migrate to the injury site, reaching peak accumulation at 1 week post-injury [5, 6]
We propose a model in which T cells contribute to early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI, but delayed tissue death limits the long-term recovery of athymic nude (AN) rats
Summary
T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. The role of the immune system in spinal cord injury (SCI) is complex, controversial, and relevant to the pathophysiology and treatment of SCI The literature supports both positive and negative effects of the immune system in functional recovery after SCI [1, 2]. Helper T cells are responsible for macrophage recruitment and activation, which has been shown to produce focal axonal injury and demyelination [7, 8]. These cells cause formation of autoimmune B cells that produce antibodies to CNS proteins [9]. Autoimmune cytotoxic T cells have been demonstrated to produce significant
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