Clonally Convergent Tph/Tfh-like CD4 + T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis

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Abstract

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures (periodontium) that requires life-long maintenance to prevent progression. Using a sensitized model of recurrent periodontitis in mice (SeRPD), in which regulatory breakdown was induced by temporary Treg depletion concurrent with disease, we mapped the gingival T cell imprint across each disease phase. Transient regulatory breakdown left a durable mucosal imprint after clinical recovery, characterized by enrichment of local and regional CD4⁺ T cells. Paired single-cell RNA and TCR sequencing of gingival immune cells identified a convergent clonotype expanded from recovery into recurrence that carried a Tfh/Tph-like transcriptional identity. An analogous CD4⁺ T cell population was detected in human periodontitis lesions by single-cell transcriptomics. Together, these findings support a paradigm in which clinical recovery does not ensure a local T cell repertoire reset; instead, a reservoir of antigen-experienced, tissue-adapted CD4⁺ T cells persist in the mucosa and participate in recurrence.

Highlights

  • The murine SeRPD model induced local and regional enrichment of antigen-experienced CD4 + T cells.

  • A clonally expanded convergent clonotype was shared in recovery and recurrence phases.

  • After clinical recovery, convergent CD4 + T clones expressed a Tfh/Tph-like program.

  • Human periodontitis lesions were associated with an analogous Tfh/Tph-like population.

In Brief

Sharma et al. show that periodontitis accompanied by regulatory breakdown, leaves a lasting, clonally expanded Tfh/Tph-like population within recovered gingiva that is also present during recurrence. A comparable CD4 + T cell-population was associated with human periodontitis, suggesting a memory reservoir for relapse.

Article activity feed

  1. Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.11.04.760965v1

  2. Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis https://www.biorxiv.org/content/10.64898/2026.11.04.760965v1

  3. Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis https://www.biorxiv.org/content/10.64898/2026.11.04.760965v1