Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis
Year: 2026
Type: preprint
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.
Authors: Apoorva Sharma, Valentina Olmedo, Leticia Rojas, Salwa Suliman, Saba Mohammadi, Katalina Lauwens, Gina Nguyen, Karina Cruz-Dwyer, Amirha Aguilar Angulo, Yahya Khan, Jennifer Dang, Connor Bluff, Nil Yakar, Stian Tornaas, Daniela-Elena Costea, Harsh Dongre, Zeliha Guney, Fatma Oner, Batbileg Bor, Shamshad Ali, Hatice Hasturk, George Hajishengallis, Keith L Kirkwood, Alpdogan Kantarci, Carla Alvarez Rivas
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: green
Award: G2434269969
OpenAlex ID: W7225324608