Intraepithelial T lymphocytes (T-IELs) are essential for protecting the intestinal barrier and facilitating a rapid immune response to local antigens. In this study, αβ T cell receptor sequencing and single-cell RNA sequencing were employed to elucidate the complex dynamics of T cells isolated from the colon epithelium and the lamina propria (LP) in three healthy human. The results reveal a significant enrichment of CD8 and γδT cells in the T-IEL population, in contrast to a predominance of CD4 cells in the LP, underscoring the presence of semi-activated antigen-experienced resident memory populations in both tissues. Differential gene expression analysis highlights an upregulation of activator protein-1 (AP-1) components, Jun and Fos, coupled with a downregulation of NF-κB subunits in both αβ CD4 and CD8 TRM cells within T-IELs, without a corresponding increase in cytokine gene transcription, as compared to LP-T cells. Gene set enrichment analysis and pseudotime analysis of LP-T and IEL-T cells from the same clones suggest the activation of an NF-κB-independent TNF pathway, concurrent with the translocation of αβT cells to the epithelium. Additionally, the LP and IEL repertoires share multiple clones, with some of the most abundant cdr3b sequences in both pools showing remarkable similarity to TCRs known to bind influenza A and CMV antigens. TCR clustering using GLIPH2 reveals common motifs across donors, yet most expanded clones in both locations possess distinct TCRs.
Navigating the Cellular Labyrinth: Unveiling the Molecular Interplay and Expansion Patterns of Intraepithelial T Lymphocytes
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Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1