γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice

Background: Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. Methods: In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (alpha beta T cells and gamma delta T cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) delta-deficient (Tcrd(-/-), lacking gamma delta T cells), and TCRa-deficient (Tcra(-/-), lacking alpha beta T cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. Results: White matter development was normal in Tcrd(-/-) and Tcra(-/-) compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcra(-/-) mice, but not in the Tcrd(-/-) mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcra(-/-) mice, but no such effect was observed in Tcrd(-/-) mice. Conclusions: Our results suggest that gamma delta T cells but not alpha beta T cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of gamma delta T cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.