Expressions of Some Neurotrophins and Neurotrophic Cytokines at Site of Spinal Cord Injury in Mice after Vaccination with Dendritic Cells Pulsed with Homogenate Proteins

Abstract

Objective: Immune cells are key mediators of secondary damage following spinal cord injury (SCI), and dendritic cell (DC)-based vaccines have received considerable interest for treatment of SCI. We previously showed that vaccination with DCs pulsed with homogenate proteins of the spinal cord (hpDCs) promotes functional recovery from SCI in mice. However, the underlying molecular mechanisms remain unclear. Here, changes of neurotrophins, cytokines and T cells at the site of SCI in mice after vaccination with hpDCs were investigated and correlated with recovery from SCI. Methods: hpDCs, DCs (control) or PBS (control) were injected intraperitoneally into injured mouse spinal cords. Functional recovery of the spinal cord was measured weekly using the Basso Mouse Scale (BMS) and confirmed by histological and immunohistochemical analysis. Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), interleukin-4 (IL-4) and interferon-γ (IFN-γ) levels in T cell culture supernatants and spinal cord tissues were determined by ELISA. Results: Eighty-four days after immunization, the BMS score of the hpDCs group (6.92 ± 0.20) was significantly higher than those of the DCs and PBS groups (p < 0.01). Meanwhile, the injury area and number of cysts in the hpDCs group decreased significantly compared with control groups. BDNF, NT-3, IL-4 and IFN-γ levels at the injured site as well as BDNF and NT-3 levels in the supernatant of cultured T cells from the hpDCs group were significantly higher than in control groups (p < 0.05). Conclusion: These results reveal that vaccination with hpDCs can promote SCI repair potentially by upregulating BDNF, NT-3, IL-4 and IFN-γ at the injury site.

Immunomodulation induced by central nervous system‐related peptides as a therapeutic strategy for neurodegenerative disorders

“…Also, it was reported that the vaccination with spinal cord homogenate‐pulsed dendritic cells 89,90 and in particular with A91‐pulsed dendritic cells 91 enhanced the expression level of BDNF and NT‐3 and exerted neuroprotective effect in a SCI mice model.…”

“…87 However, they recently observed that combined therapy of monocyte locomotion inhibitor factor, A91 peptide, and glutathione monoethyl ester (GSH-MEE) preserved spinal cord tissue integrity and promoted functional motor recovery in rats following chronicstage SCI. 88 Also, it was reported that the vaccination with spinal cord homogenate-pulsed dendritic cells 89,90 and in particular with A91pulsed dendritic cells 91 enhanced the expression level of BDNF and NT-3 and exerted neuroprotective effect in a SCI mice model.…”

Title: Immunotherapy; a ground-breaking remedy for spinal cord injury with stumbling blocks: An overview

“…Additionally, cell-based vaccination also possesses the potential to activate innate immune responses against peptides in MBP (myelin-based protein), which is likely to enhance the innate immunity (mediated by neutrophils, microglia, or macrophages) by promoting the body’s self-repair capability against antigens located at the site of injury ( Hauben and Schwartz, 2003 ). Since spinal cord injury itself could trigger self-destructive processes that result in significant damage to its function, however, immune-mediated repair and maintenance can protect against self-destructive compounds that form after a spinal cord injury ( Hauben and Schwartz, 2003 ; Wang et al, 2013 ). Accordingly, a recent study has reported that antigen-presenting cells (APCs) such as dendritic cells can mediate neuroprotection by inducing a T-cell-dependent immune response.…”

“…It thus opens up the possibility of applying antigen-specific DCs as an efficient therapeutic strategy that can modulate neuroinflammation by transiently inducing autoimmune responses. Further studies have provided evidence that DCs primed cells can potentially trigger local adaptive immunity (mediated by B- and T-cell) by systemic immunization against antigens located at the lesion site ( Wang et al, 2013 ). Thus indicating dendritic cell (DC)-based vaccines as promising treatments for SCI due to their ability to combat the effects of immune cells (pivotal mediators of secondary damage) ( Wang et al, 2013 ).…”

Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury

“…Perhaps, APC must be primed first with NMP or SC homogenate (SHC), because, even mature DCs can evoke antigen-specific T lymphocyte response, it is not efficient enough to promote motor recovery [112]. Studies support the idea that only pulsed DCs can influence the secretion of neurotrophic factors like BDNF and neurotrophin-3 (NT3) in culture supernatants and at the SC lesion site via CD4 + T lymphocyte, motoneuron survival, NSCs proliferation and functional recovery [113][114][115]. Also, A91 has been used to pulse DCs, proving that motor recovery increase since the eleven days in comparison with control rats and an autoimmune response is not developed when Lewis strain is used but apparently a T lymphocyte response is involved, because when neonatally thymectomized rats are injected DCs treatment has no effect on recovery [116].…”