gamma delta T Cells in Brain Homeostasis and Diseases

Abstract

gamma delta T cells are a distinct subset of T cells expressing gamma delta T cell receptor (TCR) rather than alpha beta TCR. Since their discovery, the critical roles of gamma delta T cells in multiple physiological systems and diseases have been investigated. gamma delta T cells are preferentially located at mucosal surfaces, such as the gut, although a small subset of gamma delta T cells can circulate the blood. Additionally, a subset of gamma delta T cells reside in the meninges in the central nervous system. Recent findings suggest gamma delta T cells in the meninges have critical roles in brain function and homeostasis. In addition, several lines of evidence have shown gamma delta T cells can infiltrate the brain parenchyma and regulate inflammatory responses in multiple diseases, including neurodegenerative diseases. Although the importance of gamma delta T cells in the brain is well established, their roles are still incompletely understood due to the complexity of their biology. Because gamma delta T cells rapidly respond to changes in brain status and regulate disease progression, understanding the role of gamma delta T cells in the brain will provide critical information that is essential for interpreting neuroimmune modulation. In this review, we summarize the complex role of gamma delta T cells in the brain and discuss future directions for research.