γδ T Cells Contribute to Injury in the Developing Brain.

Abstract

Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury 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 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 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 initiators of injury independently of common γδT-cell-associated cytokines. This finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.

• Authors: Anna-Maj Albertsson, Xiaoli Zhang, Regina Vontell, Dan Bi, Roderick T Bronson, Veena Supramaniam, Ana A Baburamani, Sha Hua, Arshed Nazmi, Susanna Cardell, Changlian Zhu, Harvey Cantor, Carina Mallard, Henrik Hagberg, Jianmei W Leavenworth, Xiaoyang Wang
• Journal: The American journal of pathology (Am J Pathol) Vol. 188 Issue 3 Pg. 757-767 (03 2018) ISSN: 1525-2191 [Electronic] United States
• PMID: 29248460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-17
• Interferon-gamma

Topics

• Animals
• Brain (metabolism, pathology)
• Disease Models, Animal
• Female
• Humans
• Hypoxia-Ischemia, Brain (metabolism, pathology)
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Intraepithelial Lymphocytes (metabolism, pathology)
• Leukomalacia, Periventricular (metabolism, pathology)
• Male
• Mice
• Sheep