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γδ T cells contribute to injury in the developing brain

Research output: Contribution to journalArticle

Anna-Maj Albertsson, Xiaoli Zhang, Regina Vontell, Dan Bi, Roderick Bronson, Veena Supramaniam, Ana Baburamani, Sha Hua, Arshed Nazmi, Susanna Cardell, Carina Mallard, Henrik Hagberg, Changlian Zhu, Harvey Cantor, Jianmei Leavenworth, Xiaoyang Wang

Original languageEnglish
Pages (from-to)757-767
JournalThe American journal of pathology
Volume188
Issue number3
Early online date15 Dec 2017
DOIs
Publication statusPublished - Mar 2018

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Abstract

Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurological disabilities. Inflammation contributes to the development of perinatal brain injury, but the essential mediators leading to brain injury in early life remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However γδT-cells are already functionally competent during early development and are important in early life immunity. We investigated the potential contribution of γδT-cells to preterm brain injury by using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury—the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT-cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT-cells provided protection in the mouse model. The common γδT-cell associated cytokines interferon-γ and interleukin (IL)-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain where, unlike injury in the mature brain, γδT-cells function as important initiators of injury independently of common γδT-cell associated cytokines. This new finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.

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