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

Journal of Experimental Medicine, 2018 · DOI: https://doi.org/10.1084/jem.20170686 · Published: February 1, 2018

Simple Explanation

This study investigates the role of γδ T cells, a subset of T cells, in spinal cord injury (SCI). It demonstrates that mice lacking γδ T cells show improved functional recovery after SCI. The research identifies that γδ T cells are present at the injury site shortly after SCI and are primarily the Vγ4 subtype, producing the inflammatory cytokine IFN-γ. Blocking IFN-γ signaling in macrophages reduces the production of pro-inflammatory cytokines and enhances functional recovery. The study also finds that treating SCI with anti-Vγ4 antibodies yields similar benefits to anti–TNF-α treatment. Moreover, γδ T cells are found in the cerebrospinal fluid of SCI patients, with most being IFN-γ positive, suggesting that manipulating γδ T cell functions could be a potential therapeutic approach for SCI.

Study Duration

8 weeks

Participants

Mice (C57BL/6J, TCRδ−/−, IFN-γ−/−, IFN-γR−/−, and TCRα+/−; TCRδEGFP/+) and 22 human SCI patients and 20 control donors

Evidence Level

Not specified

Key Findings

1
Depletion or inactivation of γδ T cells, particularly the Vγ4 subtype, in mice leads to improved functional recovery after spinal cord injury (SCI).
2
γδ T cells, specifically the Vγ4 subtype, are recruited to the injury site early after SCI and produce IFN-γ, which promotes inflammation by activating macrophages.
3
In SCI patients, γδ T cells are detected in the cerebrospinal fluid (CSF) and produce IFN-γ, suggesting a similar role in human SCI pathology.

Research Summary

This study demonstrates that γδ T cells, especially Vγ4 γδ T cells, are recruited at the injury site during the early phase after SCI, which impairs functional recovery. IFN-γ secreted by Vγ4 γδ T cells acts on BMDMs, triggering their production of TNF-α and other cytokines. Inactivation of Vγ4 γδ T cells or blocking of IFN-γ functions results in functional improvement comparable to that obtained with anti–TNF-α treatment, further confirming a detrimental role of Vγ4 γδ T cells in SCI. Detection of IFN-γ–producing γδ T cells in the CSF and peripheral blood of SCI patients lends further support to our hypothesis. Therefore, our studies demonstrate a previously unknown, physiopathological mechanism of neurological impairment after SCI and identify Vγ4 γδ T cells as novel potential therapeutic targets.

Practical Implications

Therapeutic Target Identification

Vγ4 γδ T cells are identified as a potential therapeutic target for SCI, suggesting that interventions aimed at modulating the activity or presence of these cells could improve outcomes after SCI.

Development of Novel Therapies

The study supports the development of therapies targeting Vγ4 γδ T cells or IFN-γ signaling to reduce inflammation and promote functional recovery following SCI.

Translation to Human Treatment

The presence of IFN-γ-producing γδ T cells in the CSF of SCI patients suggests that the findings in mice may be relevant to human SCI pathology, supporting the potential translation of these therapeutic strategies to clinical use.

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

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Target Identification

Development of Novel Therapies

Translation to Human Treatment

Study Limitations

Your Feedback

Was this summary helpful?

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

Simple Explanation

Key Findings

Research Summary

Practical Implications

Therapeutic Target Identification

Development of Novel Therapies

Translation to Human Treatment

Study Limitations

Your Feedback

Was this summary helpful?