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Updated: Feb 16, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
γδ T Cells Contribute to Injury in the Developing Brain
Anna-Maj Albertsson1, Xiaoli Zhang2, Regina Vontell3
1Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Gamma delta T (γδT) cells initiate brain injury in premature infants, independent of common cytokines. Depleting these cells protected mice, suggesting new therapeutic targets for neonatal brain injury.
Area of Science:
- Neuroscience
- Immunology
- Neonatal Medicine
Background:
- Perinatal brain injury, particularly periventricular leukomalacia, causes significant neurologic disabilities in premature infants.
- Inflammation is implicated in perinatal brain injury, but key mediators in early-life brain damage are not fully understood.
- Neonates have limited conventional alpha-beta T-cell responses, while gamma-delta T (γδT) cells are crucial for early immunity.
Purpose of the Study:
- To investigate the role of γδT cells in the development of preterm brain injury.
- To identify the specific mechanisms by which γδT cells contribute to neonatal brain damage.
Main Methods:
- Analysis of postmortem brains from human preterm infants with periventricular leukomalacia.
- Utilized a hypoxic-ischemic mouse model and a fetal sheep asphyxia model of preterm brain injury.
- Examined γδT cell infiltration and depletion effects in animal models, assessing cytokine production.
Main Results:
- Significant infiltration of γδT cells was observed in the brains of injured preterm infants, mice, and sheep.
- Depletion of γδT cells conferred protection in the mouse model of preterm brain injury.
- Common γδT cell cytokines (IFN-γ, IL-17A) were undetectable; IL-17F and IL-22 did not contribute to injury despite increased mRNA levels.
Conclusions:
- γδT cells act as initiators of preterm brain injury, distinct from their role in mature brain injury.
- This injury mechanism operates independently of canonical γδT cell-associated cytokines.
- Findings identify γδT cells as potential therapeutic targets for preventing or treating brain injury in premature infants.
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.
