T cell deficiency in spinal cord injury: altered locomotor recovery and whole-genome transcriptional analysis

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.

Human Schwann cells exhibit long‐term cell survival, are not tumorigenic and promote repair when transplanted into the contused spinal cord

“…Though HuSCs were transplanted at 1 month after SCI they could have still mediated protective effects on the host as ongoing changes in the evolution of injury have been reported at this time, including processes of Wallerian degeneration, demyelination and inflammation (Hagg and Oudega, ; Iizuka, Yamamoto, Iwasaki, Yamamoto, & Konno, ; Schwab, Zhang, Kopp, Brommer, & Popovich, ). In addition, the altered immunological status of the nude rat may have produced a delay in the timing of these pathological processes with the absence of T‐cell‐mediated inflammation as previously reported (Satzer et al, ). Observed differences in white matter volume could have been produced not only from a reduction in demyelination but also through an enhancement of endogenous remyelination.…”

Persons with Chronic Spinal Cord Injury Have Decreased Natural Killer Cell and Increased Toll-Like Receptor/Inflammatory Gene Expression

“…33 In athymic nude rats, which do not have T lymphocytes, NK cell markers were elevated intraspinally at 8 weeks post-injury, whereas motor recovery was only improved at 1 week post-injury, compared to Sprague-Dawley rats. 48 …”

Dynamic cell interactions allow spinal cord regeneration in zebrafish

“…Adaptive immune cells, such as T cells are thought to inhibit regeneration in mammals, as their depletion improves injury outcomes [41,42]. It has recently been shown that depletion of regulatory T cells in a spinal injury site in adult zebrafish strongly inhibits regeneration of axons, progenitor cell proliferation, addition of new neurons and functional recovery [43].…”