Brain resident memory T cells rapidly expand and initiate neuroinflammatory responses following CNS viral infection

Healthy brain harbors populations of resident memory T cells (TRM). These TRM cells rapidly proliferate in response to CNS insults of various origins. Following clearance of the insult, populations of TRM cells in the brain decline, but an antigen-specific TRM subset remains within the brain. Antige...

Full description

Saved in:
Bibliographic Details
Published in:Brain, behavior, and immunity behavior, and immunity, 2023-08, Vol.112, p.51-76
Main Authors: Ayasoufi, Katayoun, Wolf, Delaney M., Namen, Shelby L., Jin, Fang, Tritz, Zachariah P., Pfaller, Christian K., Zheng, Jiaying, Goddery, Emma N., Fain, Cori E., Gulbicki, Lauren R., Borchers, Anna L., Reesman, Rachael A., Yokanovich, Lila T., Maynes, Mark A., Bamkole, Michael A., Khadka, Roman H., Hansen, Michael J., Wu, Long-Jun, Johnson, Aaron J.
Format: Article
Language:English
Subjects:
Animals
Brain
CD8-Positive T-Lymphocytes
COVID-19
Immunologic Memory
Memory T Cells
Mice
Neuroinflammatory Diseases
Virus Diseases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Healthy brain harbors populations of resident memory T cells (TRM). These TRM cells rapidly proliferate in response to CNS insults of various origins. Following clearance of the insult, populations of TRM cells in the brain decline, but an antigen-specific TRM subset remains within the brain. Antigen-specific reactivation of brain TRMs mediates neuroinflammatory sequalae involving activation and blasting of resident T cells, infiltration of inflammatory myeloid cells, microglial activation, and blood brain barrier disruption. TRM reactivation within the brain is causal to neuropathology. Severe neuroinflammation within the brain following antigen-specific TRM reactivation is concurrent with profound lymphopenia within the blood compartment. [Display omitted] •We report that brains of naïve mice harbor populations of T cells with a resident memory phenotype that rapidly respond following neurological insults through proliferation.•Post clearance of the insult, antigen-specific TRMs are found within the brain. These TRMs remain in the brain long after clearance of the insult.•We determined that antigen-specific reactivation of TRMs, using cognate peptide delivery, induces significant infiltration of myeloid cells into the brain, activation of T-cells and microglia within the brain, significant blood-brain-barrier disruption, and peripheral lymphopenia.•Significant infiltration of myeloid cells, activation of T-cells and microglia, significant blood-brain-barrier disruption, and peripheral lymphopenia following antigen-specific CD8 TRM reactivation is mediated by TRM cells residing within the brain. These events were induced by brain TRMs, as depletion of peripheral T-cells or blocking T-cell trafficking did not change the neuroinflammatory course.•Reactivation of brain resident memory T cells, without any external trauma, is a form of neurological insult that leads to neuroinflammation and peripheral immunosuppression. The contribution of circulating verses tissue resident memory T cells (TRMs) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRMs are protective against pathogens in the brain. However, the extent to which antigen-specific TRMs induce neuropathology upon reactivation is understudied. Using the described phenotype of TRMs, we found that brains of naïve mice harbor populations of CD69+ CD103- T cells. Notably, numbers of CD69+ CD103- TRMs rapidly increase following neurological ins
ISSN:0889-1591
1090-2139
1090-2139
DOI:10.1016/j.bbi.2023.05.009