Undergraduate Student University at Buffalo, SUNY Buffalo, New York, United States
Disclosure(s):
Amirha Jhenevy Aguilar Angulo: No financial relationships to disclose
Introduction/Rationale: The oral mucosa is a major immunological barrier and a primary site of interaction between the host immune system and the oral microbiome. Periodontitis is a highly prevalent, recurrent inflammatory disease of the gingiva characterized by tissue destruction; however, the immunological mechanisms driving disease relapse remain poorly understood. We hypothesized that recurrence is driven by clonally expanded, antigen-experienced CD4⁺ memory T cells that persist in the tissue after microbial challenge resolution and retain effector programs biased toward Th1 and Th17 lineages.
Methods: We used imaging mass cytometry of human gingival samples and a mouse model of recurrent periodontitis that combined transient regulatory T cell (Treg) depletion to enhance CD4⁺ T cell recruitment without altering antigen specificity. Disease resolution was confirmed by alveolar bone micro-CT. We next performed integrated single-cell RNA sequencing, paired with T cell receptor (TCR) sequencing, of gingival cells to define transcriptional states and clonal architecture of gingival CD4⁺ T cells in disease recovery and recurrence.
Results: In human gingival samples, we identified enrichment of peri-epithelial CD45RO⁺ CD4⁺ T cells in periodontitis, consistent with retention of antigen-experienced cells. In recovered mice, there was a significant increase in gingival CD4⁺ T cell retention (p < 0.05) compared with controls. Clonally expanded CD4⁺ T cells displayed transcriptional signatures of tissue-resident memory and expression of inhibitory checkpoints associated with chronic activation. Highly expanded clonotypes persisted across recovery and recurrence and maintained stable Th1 effector programs, while acquiring Th17 features.
Conclusion: These findings implicate tissue-adapted, clonally expanded CD4⁺ T cells as potential drivers of recurrent oral mucosal inflammation and highlight adaptive immune memory as a therapeutic target for preventing periodontitis and peri-implantitis.
