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

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI).gamma delta 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 gamma delta T cells (TCR delta(-/-)) showed improved functional recovery after SCI. gamma delta T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the V gamma 4 subtype and express the inflammatory cytokine IFN-gamma. Inactivating IFN-gamma 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-V gamma 4 antibodies has a beneficial effect, similar to that obtained with anti-TNF-alpha. In SCI patients, gamma delta T cells are detected in the CSF, and most of them are IFN-gamma positive. In conclusion, manipulation of gamma delta T cell functions may be a potential approach for future SCI treatment.