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 (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd -/-, lacking γδT cells), and TCRα-deficient (Tcra -/-, lacking αβT 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 Tcrα -/- compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα -/- 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 Tcrα -/- mice, but no such effect was observed in Tcrd -/- mice.CONCLUSIONS: Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.</p

Additional file 1: of γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice

Treadmill-based measurement of gait properties. (A) A representative image from the video recording of a mouse running on the treadmill at 25 cm/s at PND26. (B) Digital print of each paw illustrated in (A). (C) Graph of paw area in contact with the treadmill surface over time for a representative single paw showing stride duration, swing duration, and stance duration. (D) The definitions for stance width, stride length, and step angle. (JPEG 227 kb