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

Sharma, A.; Olmedo, V.; Rojas, L.; Suliman, S.; Mohammadi, S.; Lauwens, K.; Nguyen, G.; Cruz-Dwyer, K.; Aguilar Angulo, A.; Khan, Y.; Dang, J.; Bluff, C.; Yakar, N.; Tornaas, S.; Costea, D.-E.; Dongre, H.; Guney, Z.; Oner, F.; Bor, B.; Ali, S.; Hasturk, H.; Hajishengallis, G.; Kirkwood, K. L.; Kantarci, A.; Alvarez Rivas, C.

doi:10.64898/2026.11.04.760965

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bioRxiv · 10.64898/2026.11.04.760965

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.

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Sharma, A., Olmedo, V., Rojas, L., Suliman, S., Mohammadi, S., Lauwens, K., Nguyen, G., Cruz-Dwyer, K., Aguilar Angulo, A., Khan, Y., Dang, J., Bluff, C., Yakar, N., Tornaas, S., Costea, D.-E., Dongre, H., Guney, Z., Oner, F., Bor, B., Ali, S., Hasturk, H., Hajishengallis, G., Kirkwood, K. L., Kantarci, A., Alvarez Rivas, C.. 2026-11-05. Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis. https://doi.org/10.64898/2026.11.04.760965

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