Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis
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.
Authors
- Fatma Öner (ORCID: https://orcid.org/0000-0001-6193-2029)
- Harsh Dongre (ORCID: https://orcid.org/0000-0003-4378-2869)
- Alpdoğan Kantarcı (ORCID: https://orcid.org/0000-0002-2679-9100)
- Batbileg Bor (ORCID: https://orcid.org/0000-0002-1797-1730)
- Nil Yakar (ORCID: https://orcid.org/0000-0002-0568-0928)
- Saba Mohammadi (ORCID: https://orcid.org/0000-0002-6957-1392)
- Daniela Elena Costea (ORCID: https://orcid.org/0000-0001-7673-0358)
- Hatice Hastürk (ORCID: https://orcid.org/0000-0002-4395-3958)
- Stian Tornaas
- Zeliha Güney (ORCID: https://orcid.org/0000-0001-6897-0773)
- Keith Lough Kirkwood (ORCID: https://orcid.org/0000-0003-4519-8973)
- Salwa Suliman (ORCID: https://orcid.org/0000-0003-0385-6157)
- George Hajishengallis (ORCID: https://orcid.org/0000-0001-7392-8852)
- Katalina Lauwens (ORCID: https://orcid.org/0009-0006-9090-9729)
- Carla Alvarez Rivas
- Valentina Olmedo (ORCID: https://orcid.org/0009-0002-8671-0179)
- Apoorva Sharma
- Amirha Aguilar Angulo
- Yahya Khan
- Leticia Rojas
- Shamshad Ali
- Jennifer Dang
- Karina Cruz-Dwyer
- Connor Bluff
- Gina Nguyen
Institutions
- University of Minnesota (US)
- The Forsyth Institute (US)
- University of Bergen (NO)
- University at Buffalo, State University of New York (US)
- University of Pennsylvania (US)
- KU Leuven (BE)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-05
- DOI
- https://doi.org/10.64898/2026.11.04.760965
- Primary Topic
- Oral microbiology and periodontitis research
- Type
- preprint