King's College London

Research portal

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

Research output: Contribution to journalArticle

Xiaoli Zhang, Eridan Rocha-Ferreira, Tao Li, Regina Vontell, Darakhshan Jabin, Sha Hua, Kai Zhou, Arshed Nazmi, Anna-Maj Albertsson, Kristina Sobotka, Joakim Ek, Claire Thornton, Henrik Hagberg, Carina Mallard, Jianmei W Leavenworth, Changlian Zhu, Xiaoyang Wang

Original languageEnglish
Pages (from-to)255
JournalJournal of neuroinflammation
Volume14
Issue number1
Early online date20 Dec 2017
DOIs
Publication statusE-pub ahead of print - 20 Dec 2017

Documents

King's Authors

Abstract

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.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454