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.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}