Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). 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 T cells ( TCR –/– ) showed improved functional recovery after SCI. T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the V4 subtype and express the inflammatory cytokine IFN-. Inactivating IFN- 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-V4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, T cells are detected in the CSF, and most of them are IFN- positive. In conclusion, manipulation of T cell functions may be a potential approach for future SCI treatment.