In Vitro Resident Memory CD8 T Cell Differentiation Using Epithelial Organoid-T Cell Co-culture System
Year: 2026
Type: article
Abstract: Barrier mucosal tissues play an important role in the differentiation and function of resident T cells. Among the diverse cell populations within these tissues, epithelial cells are key drivers of T cell differentiation. However, our understanding of the epithelial-derived signals that shape T cell biology in mucosal environments remains limited, largely due to a lack of specific tools and the complexity of available model systems. Here, we describe a murine vaginal epithelial organoid-CD8 T cell co-culture system that models dynamic interactions between infected epithelium and virus-specific CD8 T cells. This protocol enables phenotypic and functional analysis of T cell responses within a physiologically relevant three-dimensional epithelial microenvironment. Using this system, we demonstrate the differentiation of effector CD8 T cells into tissue-resident memory T cells (TRM). This versatile in vitro culture system provides reductionist opportunities to investigate molecular details of epithelial cues behind CD8 T cell differentiation that govern protective immunity and immunopathology in barrier organs.
DOI: 10.3791/69120
Authors: Ying Lin, Julian C. Ramprashad, Elizabeth L. Hillier, Lalit K. Beura
Institution: Brown University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W7127304791
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