Poster #84: Apoorva Sharma MS

A persistent clonally expanded CD4⁺ phenotype revealed by paired single-cell transcriptome and TCR-repertoire analysis in recurrent mucosal inflammation.

Sharma A*, Olmedo V, Alvarez Rivas C. Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA

T cell clonal diversity analyzes across disease states can provide important insights into disease pathology and potential interventions. By means of paired single-cell transcriptomic and TCR sequencing technologies, we elucidated the impact of temporary mucosal immune regulatory disruption in T cell clonal dynamics. We analyzed CD45+ cells from the gingiva of Foxp3DTR mice across four disease phases: health, transient immune-regulatory breakdown with periodontal disease, recovery, and disease recurrence. The cells were processed using the 10X Genomics Chromium 5’ gene expression and TCR platform. T cell subtypes were annotated and paired with clonal status using integrated transcriptomic and TCR repertoire analysis. We identified the recovery phase as the most oligoclonal, characterized by the enrichment of highly expanded, antigen-experienced CD4+ T cells with a Tph -like phenotype. Our pipeline tracked a persistent expanded TCR sequence in cells displaying a pro-inflammatory transcriptomic program in disease recurrence. In conclusion, paired single-cell sequencing technologies allowed the identification of a specific T cell subtype and its TCR sequence that is involved in disease recurrence in our model.