Influence of the intensity, level and phase of spinal cord injury on the proliferation of T cells and T-cell-dependent antibody reactions in rats

Abstract Background Immune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. γδ T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether γδ T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI. Methods Basso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes. Results In this study, we demonstrated that TCRδ−/− mice present improved neurological recovery after SCI. γδ T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2−/− and CCR2−/− mouse strains. Furthermore, reconstitution of TCRδ−/− mice with γδ T cells extracted from CCR2−/− mice also showed similar results to CCL2 and CCR2 deficient mice. Conclusions In conclusion, γδ T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of γδ T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.

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Cardiorespiratory Responses to 10 Weeks of Exoskeleton-Assisted Overground Walking Training inChronic Nonambulatory Patients with Spinal Cord Injury

Sensors ◽

10.3390/s21155022 ◽

2021 ◽

Vol 21 (15) ◽

pp. 5022

Author(s):

Jae Hyeon Park ◽

Hyeon Seong Kim ◽

Seong Ho Jang ◽

Dong Jin Hyun ◽

Sang In Park ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oxygen Consumption ◽

Exercise Intensity ◽

Moderate Physical Activity ◽

Intensity Level ◽

Cardiorespiratory System ◽

Cardiorespiratory Responses ◽

Cord Injury ◽

Walking Efficiency

Exercise intensity of exoskeleton-assisted walking in patients with spinal cord injury (SCI) has been reported as moderate. However, the cardiorespiratory responses to long-term exoskeleton-assisted walking have not been sufficiently investigated. We investigated the cardiorespiratory responses to 10 weeks of exoskeleton-assisted walking training in patients with SCI. Chronic nonambulatory patients with SCI were recruited from an outpatient clinic. Walking training with an exoskeleton was conducted three times per week for 10 weeks. Oxygen consumption and heart rate (HR) were measured during a 6-min walking test at pre-, mid-, and post-training. Exercise intensity was determined according to the metabolic equivalent of tasks (METs) for SCI and HR relative to the HR reserve (%HRR). Walking efficiency was calculated as oxygen consumption divided by walking speed. The exercise intensity according to the METs (both peak and average) corresponded to moderate physical activity and did not change after training. The %HRR demonstrated a moderate (peak %HRR) and light (average %HRR) exercise intensity level, and the average %HRR significantly decreased at post-training compared with mid-training (31.6 ± 8.9% to 24.3 ± 7.3%, p = 0.013). Walking efficiency progressively improved after training. Walking with an exoskeleton for 10 weeks may affect the cardiorespiratory system in chronic patients with SCI.

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Chapter 29 T cell-based therapeutic vaccination for spinal cord injury

Progress in Brain Research - Spinal Cord Trauma: Regeneration, Neural Repair and Functional Recovery ◽

10.1016/s0079-6123(02)37031-6 ◽

2002 ◽

pp. 401-406 ◽

Cited By ~ 15

Author(s):

Michal Schwartz ◽

Ehud Hauben

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

T Cell ◽

Therapeutic Vaccination ◽

Cord Injury

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γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury

Journal of Experimental Medicine ◽

10.1084/jem.20170686 ◽

2017 ◽

Vol 215 (2) ◽

pp. 521-535 ◽

Cited By ~ 27

Author(s):

Guodong Sun ◽

Shuxian Yang ◽

Guangchao Cao ◽

Qianghua Wang ◽

Jianlei Hao ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

T Cells ◽

Functional Recovery ◽

Γδ T Cells ◽

Small Subset ◽

Cell Functions ◽

Tnf Α ◽

Cord Injury ◽

Ifn Γ

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ−/−) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ. Inactivating IFN-γ signaling in macrophages results in a significantly reduced production of proinflammatory cytokines in the cerebrospinal fluid (CSF) of mice with SCIs and improves functional recovery. Furthermore, treatment of SCI with anti-Vγ4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, γδ T cells are detected in the CSF, and most of them are IFN-γ positive. In conclusion, manipulation of γδ T cell functions may be a potential approach for future SCI treatment.

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