AUTHOR=Netherby-Winslow Colleen S. , Ayers Katelyn N. , Lukacher Aron E. 

TITLE=Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.624144

DOI=10.3389/fimmu.2020.624144

ISSN=1664-3224

ABSTRACT=<p>Tissue-resident memory (T<sub>RM</sub>) CD8 T cells provide early frontline defense against regional pathogen reencounter. CD8 T<sub>RM</sub> are predominantly parked in nonlymphoid tissues and do not circulate. In addition to this anatomic difference, T<sub>RM</sub> are transcriptionally and phenotypically distinct from central-memory T cells (T<sub>CM</sub>) and effector-memory T cells (T<sub>EM</sub>). Moreover, T<sub>RM</sub> differ phenotypically, functionally, and transcriptionally across barrier tissues (e.g., gastrointestinal tract, respiratory tract, urogenital tract, and skin) and in non-barrier organs (e.g., brain, liver, kidney). In the brain, T<sub>RM</sub> are governed by a contextual milieu that balances T<sub>RM</sub> activation and preservation of essential post-mitotic neurons. Factors contributing to the development and maintenance of brain T<sub>RM</sub>, of which T cell receptor (TCR) signal strength and duration is a central determinant, vary depending on the infectious agent and modulation of TCR signaling by inhibitory markers that quell potentially pathogenic inflammation. This review will explore our current understanding of the context-dependent factors that drive the acquisition of brain (b)T<sub>RM</sub> phenotype and function, and discuss the contribution of T<sub>RM</sub> to promoting protective immune responses <italic>in situ</italic> while maintaining tissue homeostasis.</p>