Improved regeneration after spinal cord injury in mice lacking functional T- and B-lymphocytes

Abstract

It is widely accepted that the immune system plays important functional roles in regeneration after injury to the spinal cord. Immune response towards injury involves a complex interplay of immune system cells, such as neutrophils, macrophages and microglia, T- and B-lymphocytes. We investigated the influence of the lymphocyte component of the immune system on the locomotor outcome of severe spinal cord injury in a genetic mouse model of immune suppression. Transgenic mice lacking mature T- and B‐lymphocytes due to the recombination activating gene 2 gene deletion (RAG2−/− mice) were subjected to severe compression of the lower thoracic spinal cord, with the wild-type mice of the same inbred background serving as controls. According to both the Basso Mouse Scale score and single frame motion analysis, the RAG2−/− mice showed improved recovery in comparison to control mice at six weeks after injury. Better locomotor function was associated with enhanced catecholaminergic and cholinergic reinnervation of the spinal cord caudal to injury and increased axonal regrowth/sprouting at the site of injury. Myelination of axons in the ventral column measured as g-ratio was more extensive in RAG2−/− than in control mice 6weeks after injury. Additionally, the number of microglia/macrophages was decreased in the lumbar spinal cord of RAG2−/− mice after injury, whereas the number of astrocytes was increased compared with controls. We conclude that T- and B-lymphocytes restrict functional recovery from spinal cord injury by increasing numbers of microglia/macrophages as well as decreasing axonal sprouting and myelination.