Tissue resident memory CD8 T cell regulation of neurogenesis 2079

Abstract Description Increasing emergence of pathogens affecting the brain has made nervous system disorders the leading cause of global disease burden, highlighting the need to study immune-CNS interactions. We have shown that peripheral pathogen exposure induces tissue-resident memory (TRM) CD8 T cells in the brain, but the impact of these newly resident immune cells on brain function remains unclear. Adult neurogenesis, crucial for memory and cognition, occurs in the subgranular zone (SGZ) and subventricular zone (SVZ) and declines in aged Specific Pathogen Free (SPF) mice, correlating with brain CD8 TRM accumulation. To introduce T cells into the young adult mouse brain and mimic human pathogen exposures, we employed a model of “dirty” mice, Specific Pathogen Exposed (SPExp) mice. We found significant CD8 TRM cell enrichment at neurogenic borders in young SPExp brains. Neural stem cells (NSCs) increased in SPExp mice, but their proliferative capacity was lost, indicating quiescence. Total CD8 depletion resulted in reduced NSC numbers but restored proliferative capacity. Notably, CD8 depletion resulted in increased CD4 residency and increased MHC Class II expression on microglia. Depletion of only CD8 TRM subset enhanced NSC numbers and proliferation, suggesting their potent role in suppressing neurogenesis. These findings provide fundamental knowledge about pathogen induced CD8 TRM function in the brain and novel insights into their localized effects on CNS cell function and cognition. Funding Sources NIH/NIAID R21AI185067; NIH/NIAID R21AI178159; T32AI007260. Topic Categories Neuroimmunology (NEUR)