Triggering mouth-resident antiviral CD8+ T cells potentiates experimental periodontitis

Whether tissue-resident memory CD8+ T cells (TRM), which principally safeguard against viruses and cancer but also drive certain autoimmune and inflammatory conditions, impact periodontitis progression and severity remain unknown. We asked whether local reactivation of oral CD8+ TRM of a defined antigen specificity could exacerbate ligature-induced periodontitis (LIP), a well-established model of periodontal disease in mice.

Topical application of virus-mimicking peptides to the oral mucosa concurrent with LIP 1) intensified alveolar bone loss, 2) amplified gingival and cervical lymph node inflammation, and 3) stimulated gingival transcriptional changes in genes related to innate immune sensing and cell-mediated cytotoxicity. Therapeutic depletion of CD103-expressing oral CD8+ TRM in advance of LIP prevented exacerbation of disease. These observations provide evidence that oral CD103+ CD8+ TRM have the potential to participate in gingival inflammation, alveolar bone loss, and periodontitis.