CD8⁺ tissue-resident memory cells- do they modulate peripheral nervous system and neuroinflammation?

CD8⁺ TRM cells are indispensable for continuous surveillance of tissues and direct elimination of invading pathogens through a diverse range of effector mechanisms. They balance adhesion, metabolic adaptation, and commensal tolerance against the capacity for swift, targeted attack, using local tissue signals and immunological memory as a finely calibrated control mechanism that prevents both chronic inflammation and persistent infection. Given their strategic co-localization with the peripheral nervous system (PNS) across multiple tissues, this raises a compelling question: do CD8⁺ TRM cells actively regulate peripheral nerve function? In light of recent evidence on how chronic HIV infection influences mucosal CD8⁺ TRM cells and tissue inflammation, this article critically evaluates the existing literature to assess the evidence and potential mechanisms underlying the involvement of CD8⁺ TRM cells in peripheral nerve inflammation across diverse tissue and disease contexts.